www.keytrudahcp.com Open in urlscan Pro
2600:9000:20eb:2800:12:baea:ff40:93a1  Public Scan

Form analysis
0 forms found in the DOM

Text Content

THIS SITE IS INTENDED FOR HEALTH CARE PROFESSIONALS

I AM A HEALTH CARE PROFESSIONAL

Proceed to site


I AM A PATIENT OR CAREGIVER

Visit patient site
The information on this site is intended for health care professionals in the
United States, its territories, and Puerto Rico, and is not intended for the
general public.
 * Prescribing Information
 * Medication Guide
 * Indications

 * Ask Merck
 * Medical Information
 * Visit Patient Site
 * Chat

Menu
 * Efficacy
 * Safety
   * Selected Adverse Reactions
   * Treatment Monitoring & Management
 * Biomarker Testing
   * Biomarker Overview
   * PD⁠-⁠L1 Testing & Scoring
   * MSI/MMR Testing
 * Dosing &
   Preparation
   * Dosing
   * Preparation, Storage & Administration
   * Dose Modifications
 * Resources
   * HCP & Patient Resources
   * Patient Support Program
   * Mechanism of Action
   * Surgeon Resource Center





CLINICAL TRIAL RESULTS

Advanced NSCLC, Adjuvant, or Neoadjuvant and Adjuvant Therapy for Non⁠–⁠Small
Cell Lung Cancer (NSCLC)


FIRST-LINE COMBINATION THERAPY IN NONSQUAMOUS MNSCLC

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated
for the first-line treatment of patients with metastatic nonsquamous non⁠–⁠small
cell lung cancer (NSCLC), with no epidermal growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK) genomic tumor aberrations.


ON THIS PAGE


Clinical Findings From KEYNOTE⁠-⁠189

Study Design for KEYNOTE⁠-⁠189

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Appropriate Patients


DURABLE OVERALL SURVIVAL WITH KEYTRUDA AS FIRST-LINE COMBINATION THERAPY WITH
PLAT/PEM VS PLAT/PEM ALONE


CLINICAL FINDINGS FROM KEYNOTE⁠-⁠189


INITIAL ANALYSIS (MEDIAN FOLLOW-UP TIME: 10.5 MONTHS)1

--------------------------------------------------------------------------------

SUPERIOR OVERALL SURVIVAL WITH KEYTRUDA + PLAT/PEM VS PLAT/PEM ALONE


OVERALL SURVIVAL (OS)

KEYTRUDA + plat/pem (n=410)Plat/pem (n=206)

HR=0.49 (95% CI, 0.38–0.64; P<0.0001)A

Events Observed

127

(31%)Events Observed

108

(52%)Median OS

NOT REACHED

(95% CI, NR–NR)Median OS

11.3 MONTHS

(95% CI, 8.7–15.1)

a. HR based on the stratified Cox proportional hazard model; P value based on a
stratified log-rank test.
Plat/pem = (cisplatin or carboplatin) and pemetrexed; HR = hazard ratio; CI =
confidence interval; NR = not reached.
51%

REDUCTION IN THE RISK OF DEATH WITH KEYTRUDA + PLAT/PEM VS PLAT/PEM ALONE

HR=0.49 (95% CI, 0.38–0.64; P<0.0001)B

b. HR based on the stratified Cox proportional hazard model; P value based on a
stratified log-rank test.


PROTOCOL-SPECIFIED FINAL OS ANALYSIS (MEDIAN FOLLOW-UP TIME: 31.0 MONTHS)2

--------------------------------------------------------------------------------


OVERALL SURVIVAL (OS)

KEYTRUDA + plat/pem (n=410)Plat/pem (n=206)

HR=0.56 (95% CI, 0.46–0.69)

Median OS

22.0 MONTHS

(95% CI, 19.5–24.5)Median OS

10.6 MONTHS

(95% CI, 8.7–13.6)


EXPLORATORY ANALYSIS (MEDIAN FOLLOW-UP TIME: 64.6 MONTHS)3

--------------------------------------------------------------------------------


OVERALL SURVIVAL (OS), REGARDLESS OF PD⁠-⁠L1 EXPRESSION3

LIMITATION: This post-hoc analysis (median follow-up time: 64.6 months) in
KEYNOTE⁠-⁠189 was exploratory in nature and occurred after the
protocol-specified final analysis. No formal statistical testing was planned for
this updated analysis and, therefore, no statistical conclusions can be drawn.
Trial participants in either study arm could receive subsequent anti-cancer
therapy.

CROSSOVER RATE: 57.3% (118/206) of patients crossed over from plat/pem to
anti⁠–⁠PD⁠-⁠(L)1 therapy on (n=84) or off (n=34) study.c

Pinch to zoom & enlarge

HR=0.60 (95% CI, 0.50–0.72)


c. Some patients received >1 subsequent anti⁠–⁠PD⁠-⁠(L)1 therapy.
PD⁠-⁠L1 = programmed death ligand 1.


OVERALL SURVIVAL (OS)3

KEYTRUDA + plat/pem (n=410)Plat/pem (n=206)

HR=0.60 (95% CI, 0.50–0.72)

Events Observed

329

(80%)Events Observed

183

(89%)Median OS

22.0 MONTHS

(95% CI, 19.5–24.5)Median OS

10.6 MONTHS

(95% CI, 8.7–13.6)


EXPLORATORY ANALYSIS (MEDIAN FOLLOW-UP TIME: 64.6 MONTHS): OVERALL SURVIVAL IN
PD⁠-⁠L1 SUBGROUPS, INCLUDING PATIENTS WITH OR WITHOUT PD-L1 EXPRESSION3

--------------------------------------------------------------------------------


OVERALL SURVIVAL (OS) IN PATIENTS WITH PD⁠-⁠L1 EXPRESSION (TPS ≥1%)3

LIMITATION: KEYNOTE⁠-⁠189 was not powered to detect differences in the treatment
effect in this subgroup; therefore, results from this exploratory analysis
should be interpreted with caution because of the modest patient numbers and
potential imbalances in baseline characteristics within the subgroup.

STUDY CROSSOVER: Crossover to open-label KEYTRUDA was allowed in KEYNOTE⁠-⁠189.

Pinch to zoom & enlarge

HR=0.66 (95% CI, 0.52–0.84)D


d. HR based on Cox regression model with treatment as a covariate stratified by
PD⁠-⁠L1 status (≥1% vs <1%), platinum chemotherapy (cisplatin vs carboplatin),
and smoking status (never vs former/current).


OVERALL SURVIVAL (OS) IN PATIENTS WITHOUT PD⁠-⁠L1 EXPRESSION (TPS <1%)3

LIMITATION: KEYNOTE⁠-⁠189 was not powered to detect differences in the treatment
effect in this subgroup; therefore, results from this exploratory analysis
should be interpreted with caution because of the modest patient numbers and
potential imbalances in baseline characteristics within the subgroup.

STUDY CROSSOVER: Crossover to open-label KEYTRUDA was allowed in KEYNOTE⁠-⁠189.

Pinch to zoom & enlarge

HR=0.55 (95% CI, 0.39–0.76)E


e. HR based on Cox regression model with treatment as a covariate stratified by
PD⁠-⁠L1 status (≥1% vs <1%), platinum chemotherapy (cisplatin vs carboplatin),
and smoking status (never vs former/current).


INITIAL ANALYSIS: PFS AND ORR (MEDIAN FOLLOW-UP TIME: 10.5 MONTHS)1

--------------------------------------------------------------------------------

KEYTRUDA + PLAT/PEM DEMONSTRATED SUPERIOR PFS AND ORR VS PLAT/PEM ALONE IN AN
INITIAL ANALYSIS OF KEYNOTE⁠-⁠189


PROGRESSION-FREE SURVIVAL (PFS)

KEYTRUDA + plat/pem (n=410)Plat/pem (n=206)

HR=0.52 (95% CI, 0.43–0.64; P<0.0001)F

Events Observed

245

(60%)Events Observed

166

(81%)Median PFS

8.8 MONTHS

(95% CI, 7.6–9.2)Median PFS

4.9 MONTHS

(95% CI, 4.7–5.5)

ADDITIONAL INFORMATION

48% reduction in the risk of disease progression or death with KEYTRUDA +
plat/pem vs plat/pem alone (HR=0.52; 95% CI, 0.43–0.64; P<0.0001)f

f. HR based on the stratified Cox proportional hazard model; P value based on a
stratified log-rank test.


OBJECTIVE RESPONSE RATE (ORR): MORE THAN DOUBLED WITH KEYTRUDA + PLAT/PEM VS
PLAT/PEM ALONE

KEYTRUDA + plat/pem (n=410)Plat/pem (n=206)ORR

48%

(95% CI, 43–53)ORR

19%

(95% CI, 14–25)Complete Response

0.5%

Complete Response

0.5%

Partial Response

47%

Partial Response

18%

P<0.0001H

Median DOR

11.2 MONTHS

(range: 1.1+ – 18.0+ months)Median DOR

7.8 MONTHS

(range: 2.1+ – 16.4+ months)

g. Response: Best objective response as confirmed complete response or partial
response.
h. Based on Miettinen and Nurminen method stratified by PD⁠-⁠L1 status, platinum
chemotherapy, and smoking status.


STUDY DESIGN FOR KEYNOTE⁠-⁠189

--------------------------------------------------------------------------------


STUDY OVERVIEW1

Phase 3, randomized, multicenter, double-blind, active-controlled trial in
systemic therapy–naïve patients with metastatic nonsquamous NSCLC, regardless of
PD⁠-⁠L1 tumor expression status and with no EGFR or ALK genomic tumor
aberrations. Patients with autoimmune disease that required systemic therapy
within 2 years of treatment; a medical condition that required
immunosuppression; or patients who had received more than 30 Gy of thoracic
radiation within the prior 26 weeks were ineligible. Patients were randomized to
receive KEYTRUDA 200 mg, cisplatin or carboplatin, and pemetrexed intravenously
every 3 weeks (Q3W) for 4 cycles followed by KEYTRUDA 200 mg for up to 24 months
and pemetrexed Q3W (n=410); placebo, cisplatin or carboplatin, and pemetrexed
intravenously Q3W for 4 cycles followed by pemetrexed Q3W (n=206). Treatment
continued until progression of disease or unacceptable toxicity. Primary
efficacy outcome measures were OS and PFS assessed by blinded independent
central review (BICR) per Response Evaluation Criteria In Solid Tumors v1.1
(RECIST v1.1) (modified to follow a maximum of 10 target lesions and a maximum
of 5 target lesions per organ). Secondary efficacy outcome measures were ORR and
duration of response (DOR). ORR and DOR were also assessed by BICR per RECIST
v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5
target lesions per organ). Patients receiving chemotherapy alone who experienced
disease progression could cross over to receive KEYTRUDA as monotherapy.




NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY (NCCN GUIDELINES®)

CATEGORY 1 AND PREFERRED RECOMMENDATION REGARDLESS OF PD⁠-⁠L1 EXPRESSION4,I-K

Pembrolizumab (KEYTRUDA), in combination with pemetrexed and platinum
chemotherapy, is recommended (category 1 and preferred) as first-line treatment
for patients with metastatic nonsquamous non–small cell lung cancer (NSCLC),
with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase
(ALK) genomic tumor aberrations, regardless of PD⁠-⁠L1 expression.
i. See NCCN Guidelines® for recommendations specific to genetic alterations,
including EGFR, ALK, ROS1, BRAF, MET, KRAS, NTRK1/2/3, RET, and ERBB2 (HER2).
j. See NCCN Guidelines® for detailed recommendations, including combination
regimens, in patients with no targetable genomic tumor aberrations.
k. Pembrolizumab/(carboplatin or cisplatin)/pemetrexed is recommended (category
1 and preferred) as first-line therapy for certain patients with metastatic
nonsquamous NSCLC.

According to NCCN, preferred intervention = Intervention that is based on
superior efficacy, safety, and evidence, and, when appropriate, affordability;
Category 1 = Based upon high-level evidence, there is uniform NCCN consensus
that the intervention is appropriate.4

NCCN makes no warranties of any kind whatsoever regarding their content, use, or
application and disclaims any responsibility for their application or use in any
way.

BRAF = B-Raf proto-oncogene, serine/threonine kinase; ERBB2 = Erb-B2 receptor
tyrosine kinase 2; KRAS = KRAS proto-oncogene, GTPase; MET = MET proto-oncogene
receptor tyrosine kinase; NTRK1/2/3 = neurotrophic tyrosine receptor kinase; RET
= rearranged during transfection; ROS1 = ROS proto-oncogene 1, receptor tyrosine
kinase.

4. Referenced with permission from the NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2023. © National
Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed October
18, 2023. To view the most recent and complete version of the guidelines, go
online to NCCN.org.


APPROPRIATE PATIENTS


HYPOTHETICAL PATIENTS BASED ON THOSE STUDIED IN KEYNOTE⁠-⁠189

--------------------------------------------------------------------------------


Dana
Diagnosis

NONSQUAMOUS MNSCLC

Treatment History

NO PRIOR HISTORY OF THERAPY

EGFR/ALK

NEGATIVE

ECOG Status

1

PD⁠-⁠L1 Expression

<1%

Metastases

LIVER

Age72
GenderFemale
Physical ActivityLow
Smoking History30-pack-year history, quit 2 years ago
Family HistoryNo family history of cancer
mNSCLC = metastatic NSCLC; ECOG = Eastern Cooperative Oncology Group.

Keith
Diagnosis

NONSQUAMOUS MNSCLC

Treatment History

NO PRIOR HISTORY OF THERAPY

EGFR/ALK

NEGATIVE

ECOG Status

0

PD⁠-⁠L1 Expression

UNKNOWN

Metastases

LIVER

Age60
GenderMale
Physical ActivityHigh
Smoking HistoryNever smoked
Family HistoryInformation unknown
mNSCLC = metastatic NSCLC; ECOG = Eastern Cooperative Oncology Group.

Scott
Diagnosis

NONSQUAMOUS MNSCLC

Treatment History

NO PRIOR HISTORY OF THERAPY

EGFR/ALK

NEGATIVE

ECOG Status

1

PD⁠-⁠L1 Expression

10%

Metastases

BRAIN

Age62
GenderMale
Physical ActivityModerate
Smoking History20-pack-year history, quit 13 years ago
Family HistoryNo family history of cancer
mNSCLC = metastatic NSCLC; ECOG = Eastern Cooperative Oncology Group.


ADDITIONAL CLINICAL DATA

1L Combo Therapy – Squamous1L Monotherapy – Nonsquamous & Squamous2L Monotherapy
– Nonsquamous & SquamousNeoadjuvant Combo Therapy Followed by Adjuvant
Monotherapy After Surgery for Resectable (Tumors ≥4 cm or Node Positive)
NSCLCAdjuvant Therapy for Stage IB (T2a ≥4 cm), Stage II, or Stage IIIA NSCLC


RELATED INFORMATION

Selected Adverse ReactionsDosingPD⁠-⁠L1 Testing & Scoring


YOU MIGHT BE INTERESTED IN

ResourcesMechanism of Action


YOU MIGHT ALSO BE INTERESTED IN

Resources

MECHANISM OF ACTION

Resources

ACCESS & REIMBURSEMENT SUPPORT

1. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al; for the KEYNOTE⁠-⁠189
investigators. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung
cancer. N Engl J Med. 2018;378(22):2078–2092.
2. Rodríguez-Abreu D, Powell SF, Hochmair MJ, et al. Pemetrexed plus platinum
with or without pembrolizumab in patients with previously untreated metastatic
nonsquamous NSCLC protocol-specified final analysis from KEYNOTE-189. Ann Oncol.
2021;32(7):881-895.
3. Garassino MC, Gadgeel S, Speranza G, et al. Pembrolizumab plus pemetrexed and
platinum in nonsquamous non-small-cell lung cancer: 5-year outcomes from the
phase 3 KEYNOTE-189 study. J Clin Oncol. 2023;41(11):1992-1998.
doi:10.1200/JCO.22.01989
4. Referenced with permission from the NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2023. © National
Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed October
18, 2023. To view the most recent and complete version of the guidelines, go
online to NCCN.org.


SELECTED INDICATIONS FOR KEYTRUDA® (PEMBROLIZUMAB)


ADVANCED NSCLC, ADJUVANT, OR NEOADJUVANT AND ADJUVANT THERAPY FOR NON⁠–⁠SMALL
CELL LUNG CANCER (NSCLC)

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated
for the first-line treatment of patients with metastatic nonsquamous non⁠–⁠small
cell lung cancer (NSCLC), with no epidermal growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel
protein‑bound, is indicated for the first‑line treatment of patients with
metastatic squamous non⁠–⁠small cell lung cancer (NSCLC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of
patients with non⁠–⁠small cell lung cancer (NSCLC) expressing programmed death
ligand 1 (PD⁠-⁠L1) [tumor proportion score (TPS) ≥1%] as determined by an
FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic
lymphoma kinase (ALK) genomic tumor aberrations, and is:

 * stage III where patients are not candidates for surgical resection or
   definitive chemoradiation, or
 * metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with
metastatic non⁠–⁠small cell lung cancer (NSCLC) whose tumors express programmed
death ligand 1 (PD⁠-⁠L1) [tumor proportion score (TPS) ≥1%] as determined by an
FDA-approved test, with disease progression on or after platinum-containing
chemotherapy. Patients with epidermal growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to receiving
KEYTRUDA.

KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4
cm or node positive) non–small cell lung cancer (NSCLC) in combination with
platinum⁠-⁠containing chemotherapy as neoadjuvant treatment, and then continued
as a single agent as adjuvant treatment after surgery.

KEYTRUDA, as a single agent, is indicated for adjuvant treatment following
resection and platinum-based chemotherapy for adult patients with stage IB
(T2a ≥4 cm), II, or IIIA non–small cell lung cancer (NSCLC).


SELECTED SAFETY INFORMATION


SEVERE AND FATAL IMMUNE-MEDIATED ADVERSE REACTIONS

 * KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind
   to either the programmed death receptor-1 (PD⁠-⁠1) or the programmed death
   ligand 1 (PD⁠-⁠L1), blocking the PD⁠-⁠1/PD⁠-⁠L1 pathway, thereby removing
   inhibition of the immune response, potentially breaking peripheral tolerance
   and inducing immune-mediated adverse reactions. Immune-mediated adverse
   reactions, which may be severe or fatal, can occur in any organ system or
   tissue, can affect more than one body system simultaneously, and can occur at
   any time after starting treatment or after discontinuation of treatment.
   Important immune-mediated adverse reactions listed here may not include all
   possible severe and fatal immune-mediated adverse reactions.

 * Monitor patients closely for symptoms and signs that may be clinical
   manifestations of underlying immune-mediated adverse reactions. Early
   identification and management are essential to ensure safe use of
   anti–PD⁠-⁠1/PD⁠-⁠L1 treatments. Evaluate liver enzymes, creatinine, and
   thyroid function at baseline and periodically during treatment. For patients
   with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood
   cortisol at baseline, prior to surgery, and as clinically indicated. In cases
   of suspected immune-mediated adverse reactions, initiate appropriate workup
   to exclude alternative etiologies, including infection. Institute medical
   management promptly, including specialty consultation as appropriate.

 * Withhold or permanently discontinue KEYTRUDA depending on severity of the
   immune-mediated adverse reaction. In general, if KEYTRUDA requires
   interruption or discontinuation, administer systemic corticosteroid therapy
   (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or
   less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and
   continue to taper over at least 1 month. Consider administration of other
   systemic immunosuppressants in patients whose adverse reactions are not
   controlled with corticosteroid therapy.

IMMUNE-MEDIATED PNEUMONITIS

 * KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in
   patients who have received prior thoracic radiation. Immune-mediated
   pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA,
   including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%)
   reactions. Systemic corticosteroids were required in 67% (63/94) of patients.
   Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and
   withholding in 0.9% (26) of patients. All patients who were withheld
   reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence.
   Pneumonitis resolved in 59% of the 94 patients.

 * Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving
   KEYTRUDA as a single agent, including Grades 3–4 in 2.3% of patients.
   Patients received high-dose corticosteroids for a median duration of 10 days
   (range: 2 days to 53 months). Pneumonitis rates were similar in patients with
   and without prior thoracic radiation. Pneumonitis led to discontinuation of
   KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis,
   42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

 * Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who
   received KEYTRUDA as a single agent for adjuvant treatment of NSCLC,
   including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions.
   Patients received high-dose corticosteroids for a median duration of 10 days
   (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA
   in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54%
   interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

IMMUNE-MEDIATED COLITIS

 * KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea.
   Cytomegalovirus infection/reactivation has been reported in patients with
   corticosteroid-refractory immune-mediated colitis. In cases of
   corticosteroid-refractory colitis, consider repeating infectious workup to
   exclude alternative etiologies. Immune-mediated colitis occurred in 1.7%
   (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3
   (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required
   in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of
   patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15)
   and withholding in 0.5% (13) of patients. All patients who were withheld
   reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence.
   Colitis resolved in 85% of the 48 patients.

HEPATOTOXICITY AND IMMUNE-MEDIATED HEPATITIS

KEYTRUDA AS A SINGLE AGENT

 * KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis
   occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4
   (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic
   corticosteroids were required in 68% (13/19) of patients; additional
   immunosuppressant therapy was required in 11% of patients. Hepatitis led to
   permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9)
   of patients. All patients who were withheld reinitiated KEYTRUDA after
   symptom improvement; of these, none had recurrence. Hepatitis resolved in 79%
   of the 19 patients.

KEYTRUDA WITH AXITINIB

 * KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor
   liver enzymes before initiation of and periodically throughout treatment.
   Consider monitoring more frequently as compared to when the drugs are
   administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA
   and axitinib, and consider administering corticosteroids as needed. With the
   combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine
   aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST)
   (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine
   percent of the patients with increased ALT received systemic corticosteroids.
   In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2–4,
   n=116), ALT resolved to Grades 0–1 in 94%. Among the 92 patients who were
   rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a
   single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed
   in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24
   patients receiving both. All patients with a recurrence of ALT ≥3 ULN
   subsequently recovered from the event.

IMMUNE-MEDIATED ENDOCRINOPATHIES

ADRENAL INSUFFICIENCY

 * KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or
   higher, initiate symptomatic treatment, including hormone replacement as
   clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal
   insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA,
   including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions.
   Systemic corticosteroids were required in 77% (17/22) of patients; of these,
   the majority remained on systemic corticosteroids. Adrenal insufficiency led
   to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3%
   (8) of patients. All patients who were withheld reinitiated KEYTRUDA after
   symptom improvement.

HYPOPHYSITIS

 * KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present
   with acute symptoms associated with mass effect such as headache,
   photophobia, or visual field defects. Hypophysitis can cause hypopituitarism.
   Initiate hormone replacement as indicated. Withhold or permanently
   discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6%
   (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3
   (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required
   in 94% (16/17) of patients; of these, the majority remained on systemic
   corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in
   0.1% (4) and withholding in 0.3% (7) of patients. All patients who were
   withheld reinitiated KEYTRUDA after symptom improvement.

THYROID DISORDERS

 * KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present
   with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism.
   Initiate hormone replacement for hypothyroidism or institute medical
   management of hyperthyroidism as clinically indicated. Withhold or
   permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred
   in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%).
   None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.
 * Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA,
   including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent
   discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of
   patients. All patients who were withheld reinitiated KEYTRUDA after symptom
   improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving
   KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent
   discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of
   patients. All patients who were withheld reinitiated KEYTRUDA after symptom
   improvement. The majority of patients with hypothyroidism required long-term
   thyroid hormone replacement. The incidence of new or worsening hypothyroidism
   was higher in 1185 patients with HNSCC, occurring in 16% of patients
   receiving KEYTRUDA as a single agent or in combination with platinum and FU,
   including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening
   hypothyroidism was higher in 389 adult patients with cHL (17%) receiving
   KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%)
   hypothyroidism. The incidence of new or worsening hyperthyroidism was higher
   in 580 patients with resected NSCLC, occurring in 11% of patients receiving
   KEYTRUDA as a single agent as adjuvant treatment, including Grade 3 (0.2%)
   hyperthyroidism. The incidence of new or worsening hypothyroidism was higher
   in 580 patients with resected NSCLC, occurring in 22% of patients receiving
   KEYTRUDA as a single agent as adjuvant treatment (KEYNOTE⁠-⁠091), including
   Grade 3 (0.3%) hypothyroidism.

TYPE 1 DIABETES MELLITUS (DM), WHICH CAN PRESENT WITH DIABETIC KETOACIDOSIS

 * Monitor patients for hyperglycemia or other signs and symptoms of diabetes.
   Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA
   depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients
   receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and
   withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were
   withheld reinitiated KEYTRUDA after symptom improvement.

IMMUNE-MEDIATED NEPHRITIS WITH RENAL DYSFUNCTION

 * KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis
   occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4
   (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic
   corticosteroids were required in 89% (8/9) of patients. Nephritis led to
   permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3)
   of patients. All patients who were withheld reinitiated KEYTRUDA after
   symptom improvement; of these, none had recurrence. Nephritis resolved in 56%
   of the 9 patients.

IMMUNE-MEDIATED DERMATOLOGIC ADVERSE REACTIONS

 * KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative
   dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia
   and systemic symptoms, and toxic epidermal necrolysis, has occurred
   with anti–PD⁠-⁠1/PD⁠-⁠L1 treatments. Topical emollients and/or topical
   corticosteroids may be adequate to treat mild to moderate nonexfoliative
   rashes. Withhold or permanently discontinue KEYTRUDA depending on severity.
   Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of
   patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%)
   reactions. Systemic corticosteroids were required in 40% (15/38) of patients.
   These reactions led to permanent discontinuation in 0.1% (2) and withholding
   of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld
   reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence.
   The reactions resolved in 79% of the 38 patients.

OTHER IMMUNE-MEDIATED ADVERSE REACTIONS

 * The following clinically significant immune-mediated adverse reactions
   occurred at an incidence of <1% (unless otherwise noted) in patients who
   received KEYTRUDA or were reported with the use of
   other anti–PD⁠-⁠1/PD⁠-⁠L1 treatments. Severe or fatal cases have been
   reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis,
   pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis
   and demyelination, myasthenic syndrome/myasthenia gravis (including
   exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
   neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities
   can occur. Some cases can be associated with retinal detachment. Various
   grades of visual impairment, including blindness, can occur. If uveitis
   occurs in combination with other immune-mediated adverse reactions, consider
   a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with
   systemic steroids to reduce the risk of permanent vision
   loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase
   and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective
   Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae,
   including renal failure), arthritis (1.5%), polymyalgia
   rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic
   anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic
   inflammatory response syndrome, histiocytic necrotizing lymphadenitis
   (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid
   organ transplant rejection, other transplant (including corneal graft)
   rejection.


INFUSION-RELATED REACTIONS

 * KEYTRUDA can cause severe or life-threatening infusion-related reactions,
   including hypersensitivity and anaphylaxis, which have been reported in 0.2%
   of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of
   infusion-related reactions. Interrupt or slow the rate of infusion for Grade
   1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and
   permanently discontinue KEYTRUDA.


COMPLICATIONS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)

 * Fatal and other serious complications can occur in patients who receive
   allogeneic HSCT before or after anti–PD⁠-⁠1/PD⁠-⁠L1 treatments.
   Transplant-related complications include hyperacute graft-versus-host disease
   (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced
   intensity conditioning, and steroid-requiring febrile syndrome (without an
   identified infectious cause). These complications may occur despite
   intervening therapy between anti–PD⁠-⁠1/PD⁠-⁠L1 treatments and allogeneic
   HSCT. Follow patients closely for evidence of these complications and
   intervene promptly. Consider the benefit vs risks of
   using anti–PD⁠-⁠1/PD⁠-⁠L1 treatments prior to or after an allogeneic HSCT.


INCREASED MORTALITY IN PATIENTS WITH MULTIPLE MYELOMA

 * In trials in patients with multiple myeloma, the addition of KEYTRUDA to a
   thalidomide analogue plus dexamethasone resulted in increased mortality.
   Treatment of these patients with an anti–PD⁠-⁠1/PD⁠-⁠L1 treatment in this
   combination is not recommended outside of controlled trials.


EMBRYOFETAL TOXICITY

 * Based on its mechanism of action, KEYTRUDA can cause fetal harm when
   administered to a pregnant woman. Advise women of this potential risk. In
   females of reproductive potential, verify pregnancy status prior to
   initiating KEYTRUDA and advise them to use effective contraception during
   treatment and for 4 months after the last dose.


ADVERSE REACTIONS

 * In KEYNOTE⁠-⁠006, KEYTRUDA was discontinued due to adverse reactions in 9% of
   555 patients with advanced melanoma; adverse reactions leading to permanent
   discontinuation in more than one patient were colitis (1.4%), autoimmune
   hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
   cardiac failure (0.4%). The most common adverse reactions (≥20%) with
   KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

 * In KEYNOTE⁠-⁠054, when KEYTRUDA was administered as a single agent to
   patients with stage III melanoma, KEYTRUDA was permanently discontinued due
   to adverse reactions in 14% of 509 patients; the most common (≥1%) were
   pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse
   reactions occurred in 25% of patients receiving KEYTRUDA. The most common
   adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE⁠-⁠716,
   when KEYTRUDA was administered as a single agent to patients with stage IIB
   or IIC melanoma, adverse reactions occurring in patients with stage IIB or
   IIC melanoma were similar to those occurring in 1011 patients with stage III
   melanoma from KEYNOTE⁠-⁠054.

 * In KEYNOTE⁠-⁠189, when KEYTRUDA was administered with pemetrexed and platinum
   chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due
   to adverse reactions in 20% of 405 patients. The most common adverse
   reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis
   (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%)
   with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea
   (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%),
   dyspnea (21%), and pyrexia (20%).

 * In KEYNOTE⁠-⁠407, when KEYTRUDA was administered with carboplatin and either
   paclitaxel or paclitaxel protein‑bound in metastatic squamous NSCLC, KEYTRUDA
   was discontinued due to adverse reactions in 15% of 101 patients. The most
   frequent serious adverse reactions reported in at least 2% of patients were
   febrile neutropenia, pneumonia, and urinary tract infection. Adverse
   reactions observed in KEYNOTE⁠-⁠407 were similar to those observed in
   KEYNOTE⁠-⁠189 with the exception that increased incidences of alopecia (47%
   vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA
   and chemotherapy arm compared to the placebo and chemotherapy arm in
   KEYNOTE⁠-⁠407.

 * In KEYNOTE⁠-⁠042, KEYTRUDA was discontinued due to adverse reactions in 19%
   of 636 patients with advanced NSCLC; the most common were pneumonitis (3%),
   death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent
   serious adverse reactions reported in at least 2% of patients were pneumonia
   (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion
   (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

 * In KEYNOTE⁠-⁠010, KEYTRUDA monotherapy was discontinued due to adverse
   reactions in 8% of 682 patients with metastatic NSCLC; the most common was
   pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased
   appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

 * In KEYNOTE⁠-⁠671, adverse reactions occurring in patients with resectable
   NSCLC receiving KEYTRUDA in combination with platinum-containing
   chemotherapy, given as neoadjuvant treatment and continued as single-agent
   adjuvant treatment, were generally similar to those occurring in patients in
   other clinical trials across tumor types receiving KEYTRUDA in combination
   with chemotherapy.

 * The most common adverse reactions (reported in ≥20%) in patients receiving
   KEYTRUDA in combination with chemotherapy were fatigue/asthenia, nausea,
   constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea,
   pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis,
   headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia,
   palmar-plantar erythrodysesthesia, urinary tract infection, and
   hypothyroidism.

 * In the neoadjuvant phase of KEYNOTE⁠-⁠671, when KEYTRUDA was administered in
   combination with platinum-containing chemotherapy as neoadjuvant treatment,
   serious adverse reactions occurred in 34% of 396 patients. The most frequent
   (≥2%) serious adverse reactions were pneumonia (4.8%), venous thromboembolism
   (3.3%), and anemia (2%). Fatal adverse reactions occurred in 1.3% of
   patients, including death due to unknown cause (0.8%), sepsis (0.3%), and
   immune-mediated lung disease (0.3%). Permanent discontinuation of any study
   drug due to an adverse reaction occurred in 18% of patients who received
   KEYTRUDA in combination with platinum-containing chemotherapy; the most
   frequent adverse reactions (≥1%) that led to permanent discontinuation of any
   study drug were acute kidney injury (1.8%), interstitial lung disease (1.8%),
   anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%).

 * Of the KEYTRUDA-treated patients who received neoadjuvant treatment, 6% of
   396 patients did not receive surgery due to adverse reactions. The most
   frequent (≥1%) adverse reaction that led to cancellation of surgery in the
   KEYTRUDA arm was interstitial lung disease (1%).

 * In the adjuvant phase of KEYNOTE⁠-⁠671, when KEYTRUDA was administered as a
   single agent as adjuvant treatment, serious adverse reactions occurred in 14%
   of 290 patients. The most frequent serious adverse reaction was pneumonia
   (3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred.
   Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in
   12% of patients who received KEYTRUDA as a single agent, given as adjuvant
   treatment; the most frequent adverse reactions (≥1%) that led to permanent
   discontinuation of KEYTRUDA were diarrhea (1.7%), interstitial lung disease
   (1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain
   (1%).

 * Adverse reactions observed in KEYNOTE⁠-⁠091 were generally similar to those
   occurring in other patients with NSCLC receiving KEYTRUDA as a single agent,
   with the exception of hypothyroidism (22%), hyperthyroidism (11%), and
   pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.

 * In KEYNOTE⁠-⁠048, KEYTRUDA monotherapy was discontinued due to adverse events
   in 12% of 300 patients with HNSCC; the most common adverse reactions leading
   to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The
   most common adverse reactions (≥20%) were fatigue (33%), constipation (20%),
   and rash (20%).

 * In KEYNOTE⁠-⁠048, when KEYTRUDA was administered in combination with platinum
   (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due
   to adverse reactions in 16% of 276 patients with HNSCC. The most common
   adverse reactions resulting in permanent discontinuation of KEYTRUDA were
   pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most
   common adverse reactions (≥20%) were nausea (51%), fatigue (49%),
   constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea
   (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

 * In KEYNOTE⁠-⁠012, KEYTRUDA was discontinued due to adverse reactions in 17%
   of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of
   patients. The most frequent serious adverse reactions reported in at least 2%
   of patients were pneumonia, dyspnea, confusional state, vomiting, pleural
   effusion, and respiratory failure. The most common adverse reactions (≥20%)
   were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in
   patients with HNSCC were generally similar to those occurring in patients
   with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the
   exception of increased incidences of facial edema and new or worsening
   hypothyroidism.

 * In KEYNOTE⁠-⁠204, KEYTRUDA was discontinued due to adverse reactions in 14%
   of 148 patients with cHL. Serious adverse reactions occurred in 30% of
   patients receiving KEYTRUDA; those ≥1% were pneumonitis, pneumonia, pyrexia,
   myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three
   patients died from causes other than disease progression: 2 from
   complications after allogeneic HSCT and 1 from unknown cause. The most common
   adverse reactions (≥20%) were upper respiratory tract infection (41%),
   musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash, and
   cough (20% each).

 * In KEYNOTE⁠-⁠087, KEYTRUDA was discontinued due to adverse reactions in 5% of
   210 patients with cHL. Serious adverse reactions occurred in 16% of patients;
   those ≥1% were pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes
   zoster. Two patients died from causes other than disease progression: 1 from
   GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most
   common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough
   (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

 * In KEYNOTE⁠-⁠170, KEYTRUDA was discontinued due to adverse reactions in 8% of
   53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients
   and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction
   (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients
   died within 30 days of start of treatment. The most common adverse reactions
   (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and
   pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

 * In KEYNOTE⁠-⁠A39, when KEYTRUDA was administered in combination with
   enfortumab vedotin to patients with locally advanced or metastatic urothelial
   cancer (n=440), fatal adverse reactions occurred in 3.9% of patients,
   including acute respiratory failure (0.7%), pneumonia (0.5%), and
   pneumonitis/ILD (0.2%). Serious adverse reactions occurred in 50% of patients
   receiving KEYTRUDA in combination with enfortumab vedotin; the serious
   adverse reactions in ≥2% of patients were rash (6%), acute kidney injury
   (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea
   (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Permanent
   discontinuation of KEYTRUDA occurred in 27% of patients. The most common
   adverse reactions (≥2%) resulting in permanent discontinuation of KEYTRUDA
   were pneumonitis/ILD (4.8%) and rash (3.4%). The most common adverse
   reactions (≥20%) occurring in patients treated with KEYTRUDA in combination
   with enfortumab vedotin were rash (68%), peripheral neuropathy (67%), fatigue
   (51%), pruritus (41%), diarrhea (38%), alopecia (35%), weight loss (33%),
   decreased appetite (33%), nausea (26%), constipation (26%), dry eye (24%),
   dysgeusia (21%), and urinary tract infection (21%).

 * In KEYNOTE⁠-⁠052, KEYTRUDA was discontinued due to adverse reactions in 11%
   of 370 patients with locally advanced or metastatic urothelial carcinoma.
   Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary
   tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.
   The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal
   pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and
   diarrhea (20%).

 * In KEYNOTE⁠-⁠045, KEYTRUDA was discontinued due to adverse reactions in 8% of
   266 patients with locally advanced or metastatic urothelial carcinoma. The
   most common adverse reaction resulting in permanent discontinuation of
   KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of
   KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia,
   anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients
   who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%),
   pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

 * In KEYNOTE⁠-⁠057, KEYTRUDA was discontinued due to adverse reactions in 11%
   of 148 patients with high-risk NMIBC. The most common adverse reaction
   resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%).
   Serious adverse reactions occurred in 28% of patients; those ≥2% were
   pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%),
   sepsis (2%), and urinary tract infection (2%). The most common adverse
   reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

 * Adverse reactions occurring in patients with MSI⁠-⁠H or dMMR CRC were similar
   to those occurring in patients with melanoma or NSCLC who received KEYTRUDA
   as a monotherapy.

 * In KEYNOTE⁠-⁠158 and KEYNOTE⁠-⁠164, adverse reactions occurring in patients
   with MSI⁠-⁠H or dMMR cancer were similar to those occurring in patients with
   other solid tumors who received KEYTRUDA as a single agent.

 * In KEYNOTE⁠-⁠859, when KEYTRUDA was administered in combination with
   fluoropyrimidine- and platinum-containing chemotherapy, serious adverse
   reactions occurred in 45% of 785 patients. Serious adverse reactions in >2%
   of patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%),
   and vomiting (2.4%). Fatal adverse reactions occurred in 8% of patients who
   received KEYTRUDA, including infection (2.3%) and thromboembolism (1.3%).
   KEYTRUDA was permanently discontinued due to adverse reactions in 15% of
   patients. The most common adverse reactions resulting in permanent
   discontinuation of KEYTRUDA (≥1%) were infections (1.8%) and diarrhea (1.0%).
   The most common adverse reactions (reported in ≥20%) in patients receiving
   KEYTRUDA in combination with chemotherapy were peripheral neuropathy (47%),
   nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased
   appetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia
   syndrome (25%), constipation (22%), and weight loss (20%).

 * In KEYNOTE⁠-⁠590, when KEYTRUDA was administered with cisplatin and
   fluorouracil to patients with metastatic or locally advanced esophageal or
   GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who
   were not candidates for surgical resection or definitive chemoradiation,
   KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients.
   The most common adverse reactions resulting in permanent discontinuation of
   KEYTRUDA (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and
   pneumonia (1.1%). The most common adverse reactions (≥20%) with KEYTRUDA in
   combination with chemotherapy were nausea (67%), fatigue (57%), decreased
   appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%),
   stomatitis (27%), and weight loss (24%).

 * Adverse reactions occurring in patients with esophageal cancer who received
   KEYTRUDA as a monotherapy were similar to those occurring in patients with
   melanoma or NSCLC who received KEYTRUDA as a monotherapy.

 * In KEYNOTE⁠-⁠A18, when KEYTRUDA was administered with CRT (cisplatin plus
   external beam radiation therapy [EBRT] followed by brachytherapy [BT]) to
   patients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse
   reactions occurred in 1.4% of 292 patients, including 1 case each (0.3%) of
   large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage.
   Serious adverse reactions occurred in 30% of patients; those ≥1% included
   urinary tract infection (2.7%), urosepsis (1.4%), and sepsis (1%). KEYTRUDA
   was discontinued for adverse reactions in 7% of patients. The most common
   adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea
   (1%). For patients treated with KEYTRUDA in combination with CRT, the most
   common adverse reactions (≥10%) were nausea (56%), diarrhea (50%), vomiting
   (33%), urinary tract infection (32%), fatigue (26%), hypothyroidism (20%),
   constipation (18%), decreased appetite and weight loss (17% each), abdominal
   pain and pyrexia (12% each), hyperthyroidism, dysuria, rash (11% each), and
   pelvic pain (10%).

 * In KEYNOTE⁠-⁠826, when KEYTRUDA was administered in combination with
   paclitaxel and cisplatin or paclitaxel and carboplatin, with or without
   bevacizumab (n=307), to patients with persistent, recurrent, or first-line
   metastatic cervical cancer regardless of tumor PD⁠-⁠L1 expression who had not
   been treated with chemotherapy except when used concurrently as a
   radio-sensitizing agent, fatal adverse reactions occurred in 4.6% of
   patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to
   unknown causes, and 1 case each of acute myocardial infarction, autoimmune
   encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with
   perioperative pulmonary embolus, intestinal perforation, and pelvic
   infection. Serious adverse reactions occurred in 50% of patients receiving
   KEYTRUDA in combination with chemotherapy with or without bevacizumab; those
   ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia
   (4.6%), and acute kidney injury and sepsis (3.3% each).

 * KEYTRUDA was discontinued in 15% of patients due to adverse reactions. The
   most common adverse reaction resulting in permanent discontinuation (≥1%) was
   colitis (1%).

 * For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196),
   the most common adverse reactions (≥20%) were peripheral neuropathy (62%),
   alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia
   (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each),
   constipation and arthralgia (31% each), vomiting (30%), urinary tract
   infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and
   decreased appetite (21%).

 * For patients treated with KEYTRUDA in combination with chemotherapy with or
   without bevacizumab, the most common adverse reactions (≥20%) were peripheral
   neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea
   (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and
   urinary tract infection (24% each), and rash (22%).

 * In KEYNOTE⁠-⁠158, KEYTRUDA was discontinued due to adverse reactions in 8% of
   98 patients with previously treated recurrent or metastatic cervical cancer.
   Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the
   most frequent included anemia (7%), fistula, hemorrhage, and infections
   [except urinary tract infections] (4.1% each). The most common adverse
   reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea
   (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

 * In KEYNOTE⁠-⁠966, when KEYTRUDA was administered in combination with
   gemcitabine and cisplatin, KEYTRUDA was discontinued for adverse reactions in
   15% of 529 patients with locally advanced unresectable or metastatic biliary
   tract cancer. The most common adverse reaction resulting in permanent
   discontinuation of KEYTRUDA (≥1%) was pneumonitis (1.3%). Adverse reactions
   leading to the interruption of KEYTRUDA occurred in 55% of patients. The most
   common adverse reactions or laboratory abnormalities leading to interruption
   of KEYTRUDA (≥2%) were decreased neutrophil count (18%), decreased platelet
   count (10%), anemia (6%), decreased white blood cell count (4%), pyrexia
   (3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased
   AST (2.5%), and biliary obstruction (2.3%).

 * In KEYNOTE⁠-⁠017 and KEYNOTE⁠-⁠913, adverse reactions occurring in patients
   with MCC (n=105) were generally similar to those occurring in patients with
   melanoma or NSCLC who received KEYTRUDA as a single agent.

 * In KEYNOTE⁠-⁠426, when KEYTRUDA was administered in combination with
   axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious
   adverse reactions occurred in 40% of patients, the most frequent (≥1%) were
   hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration
   (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse
   reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only
   (13%), and the combination (8%); the most common were hepatotoxicity (13%),
   diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular
   accident (1.2%). The most common adverse reactions (≥20%) were diarrhea
   (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%),
   hypothyroidism (35%), decreased appetite (30%), palmar-plantar
   erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation
   (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

 * In KEYNOTE⁠-⁠564, when KEYTRUDA was administered as a single agent for the
   adjuvant treatment of renal cell carcinoma, serious adverse reactions
   occurred in 20% of patients receiving KEYTRUDA; the serious adverse reactions
   (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis,
   and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2%
   including 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse
   reactions occurred in 21% of 488 patients; the most common (≥1%) were
   increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most
   common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue
   (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

 * In KEYNOTE⁠-⁠868, when KEYTRUDA was administered in combination with
   chemotherapy (paclitaxel and carboplatin) to patients with advanced or
   recurrent endometrial carcinoma (n=759), serious adverse reactions occurred
   in 35% of patients receiving KEYTRUDA in combination with chemotherapy,
   compared to 19% of patients receiving placebo in combination with
   chemotherapy. Fatal adverse reactions occurred in 1.6% of patients receiving
   KEYTRUDA in combination with chemotherapy, including COVID-19 (0.5%) and
   cardiac arrest (0.3%). KEYTRUDA was discontinued for an adverse reaction in
   14% of patients. Adverse reactions occurring in patients treated with
   KEYTRUDA and chemotherapy were generally similar to those observed with
   KEYTRUDA alone or chemotherapy alone, with the exception of rash (33% all
   Grades; 2.9% Grades 3-4).

 * Adverse reactions occurring in patients with MSI⁠-⁠H or dMMR endometrial
   carcinoma who received KEYTRUDA as a single agent were similar to those
   occurring in patients with melanoma or NSCLC who received KEYTRUDA as a
   single agent.

 * Adverse reactions occurring in patients with recurrent or metastatic cSCC or
   locally advanced cSCC were similar to those occurring in patients with
   melanoma or NSCLC who received KEYTRUDA as a monotherapy.

 * In KEYNOTE⁠-⁠522, when KEYTRUDA was administered with neoadjuvant
   chemotherapy (carboplatin and paclitaxel followed by doxorubicin or
   epirubicin and cyclophosphamide) followed by surgery and continued adjuvant
   treatment with KEYTRUDA as a single agent (n=778) to patients with newly
   diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse
   reactions occurred in 0.9% of patients, including 1 each of adrenal crisis,
   autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary
   embolism, and sepsis in association with multiple organ dysfunction syndrome
   and myocardial infarction. Serious adverse reactions occurred in 44% of
   patients receiving KEYTRUDA; those ≥2% were febrile neutropenia (15%),
   pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). KEYTRUDA was
   discontinued in 20% of patients due to adverse reactions. The most common
   reactions (≥1%) resulting in permanent discontinuation were increased ALT
   (2.7%), increased AST (1.5%), and rash (1%). The most common adverse
   reactions (≥20%) in patients receiving KEYTRUDA were fatigue (70%), nausea
   (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and
   peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache
   (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%),
   decreased appetite (23%), insomnia (21%), and myalgia (20%).

 * In KEYNOTE⁠-⁠355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel
   protein⁠-⁠bound, or gemcitabine and carboplatin) were administered to
   patients with locally recurrent unresectable or metastatic TNBC who had not
   been previously treated with chemotherapy in the metastatic setting (n=596),
   fatal adverse reactions occurred in 2.5% of patients, including
   cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse
   reactions occurred in 30% of patients receiving KEYTRUDA in combination with
   chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia
   (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of
   patients due to adverse reactions. The most common reactions resulting in
   permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST
   (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in
   patients receiving KEYTRUDA in combination with chemotherapy were fatigue
   (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each),
   vomiting and rash (26% each), cough (23%), decreased appetite (21%), and
   headache (20%).


LACTATION

 * Because of the potential for serious adverse reactions in breastfed children,
   advise women not to breastfeed during treatment and for 4 months after the
   last dose.


PEDIATRIC USE

 * In KEYNOTE⁠-⁠051, 173 pediatric patients (65 pediatric patients aged 6 months
   to younger than 12 years and 108 pediatric patients aged 12 years to 17
   years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration
   of exposure was 2.1 months (range: 1 day to 25 months).

 * Adverse reactions that occurred at a ≥10% higher rate in pediatric patients
   when compared to adults were pyrexia (33%), leukopenia (31%), vomiting (29%),
   neutropenia (28%), headache (25%), abdominal pain (23%), thrombocytopenia
   (22%), Grade 3 anemia (17%), decreased lymphocyte count (13%), and decreased
   white blood cell count (11%).

Geriatric Use
 * Of the 564 patients with locally advanced or metastatic urothelial cancer
   treated with KEYTRUDA in combination with enfortumab vedotin, 44% (n=247)
   were 65-74 years and 26% (n=144) were 75 years or older. No overall
   differences in safety or effectiveness were observed between patients 65
   years of age or older and younger patients. Patients 75 years of age or older
   treated with KEYTRUDA in combination with enfortumab vedotin experienced a
   higher incidence of fatal adverse reactions than younger patients. The
   incidence of fatal adverse reactions was 4% in patients younger than 75 and
   7% in patients 75 years or older.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; BT =
brachytherapy; BTC = biliary tract cancer; cHL = classical Hodgkin lymphoma; CRC
= colorectal cancer; CRT = chemoradiotherapy; cSCC = cutaneous squamous cell
carcinoma; dMMR = mismatch repair deficient; EBRT = external beam radiation
therapy; FIGO = International Federation of Gynecology and Obstetrics; FU =
fluorouracil; GEJ = gastroesophageal junction; HER2 = human epidermal growth
factor receptor 2; HNSCC = head and neck squamous cell carcinoma; ILD =
interstitial lung disease; MCC = Merkel cell carcinoma; MSI⁠-⁠H = microsatellite
instability-high; NMIBC = non-muscle invasive bladder cancer; NSCLC = non–small
cell lung cancer; PMBCL = primary mediastinal large B-cell lymphoma; TNBC =
triple-negative breast cancer.

BEFORE PRESCRIBING KEYTRUDA® (PEMBROLIZUMAB), PLEASE READ THE ACCOMPANYING
PRESCRIBING INFORMATION. THE MEDICATION GUIDE ALSO IS AVAILABLE.

Visit Patient Site
Contact Us


 * EFFICACY INFORMATION

 * Efficacy


 * SAFETY

 * Selected Adverse Reactions
 * Treatment Monitoring & Management


 * BIOMARKER TESTING

 * Biomarker Overview
 * PD-L1 Testing & Scoring
 * MSI/MMR Testing


 * DOSING & PREPARATION

 * Dosing
 * Preparation, Storage & Administration
 * Dose Modifications


 * RESOURCES

 * HCP & Patient Resources
 * Patient Support Program
 * Mechanism of Action
 * Surgeon Resource Center

--------------------------------------------------------------------------------

Privacy PolicyTerms of UseSite MapCookie PreferencesAccessibility

--------------------------------------------------------------------------------

This site is intended for health care professionals of the United States, its
territories, and Puerto Rico. Copyright © 2024 Merck & Co., Inc., Rahway, NJ,
USA and its affiliates. All rights reserved.
US-LAM-03257 11/23

Selected Indications
KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12
years and older) patients with stage IIB, IIC, or III melanoma following
complete resection.


SELECTED INDICATIONS

For KEYTRUDA® (pembrolizumab)
Close


ADVANCED MELANOMA OR ADJUVANT THERAPY FOR MELANOMA

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12
years and older) patients with stage IIB, IIC, or III melanoma following
complete resection.


ADVANCED NSCLC, ADJUVANT, OR NEOADJUVANT AND ADJUVANT THERAPY FOR NON⁠–⁠SMALL
CELL LUNG CANCER (NSCLC)

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated
for the first-line treatment of patients with metastatic nonsquamous non⁠–⁠small
cell lung cancer (NSCLC), with no epidermal growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel
protein‑bound, is indicated for the first‑line treatment of patients with
metastatic squamous non⁠–⁠small cell lung cancer (NSCLC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of
patients with non⁠–⁠small cell lung cancer (NSCLC) expressing programmed death
ligand 1 (PD⁠-⁠L1) [tumor proportion score (TPS) ≥1%] as determined by an
FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic
lymphoma kinase (ALK) genomic tumor aberrations, and is:

 * stage III where patients are not candidates for surgical resection or
   definitive chemoradiation, or
 * metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with
metastatic non⁠–⁠small cell lung cancer (NSCLC) whose tumors express programmed
death ligand 1 (PD⁠-⁠L1) [tumor proportion score (TPS) ≥1%] as determined by an
FDA-approved test, with disease progression on or after platinum-containing
chemotherapy. Patients with epidermal growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to receiving
KEYTRUDA.

KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4
cm or node positive) non–small cell lung cancer (NSCLC) in combination with
platinum⁠-⁠containing chemotherapy as neoadjuvant treatment, and then continued
as a single agent as adjuvant treatment after surgery.

KEYTRUDA, as a single agent, is indicated for adjuvant treatment following
resection and platinum-based chemotherapy for adult patients with stage IB
(T2a ≥4 cm), II, or IIIA non–small cell lung cancer (NSCLC).


ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC)

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for
the first-line treatment of patients with metastatic or with unresectable,
recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of
patients with metastatic or with unresectable, recurrent head and neck squamous
cell carcinoma (HNSCC) whose tumors express programmed death ligand 1 (PD⁠-⁠L1)
[combined positive score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with
recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with
disease progression on or after platinum-containing chemotherapy.


RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA (CHL)

KEYTRUDA is indicated for the treatment of adult patients with relapsed or
refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory
classical Hodgkin lymphoma (cHL), or cHL that has relapsed after 2 or more lines
of therapy.


REFRACTORY OR RELAPSED PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA (PMBCL)

KEYTRUDA is indicated for the treatment of adult and pediatric patients with
refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have
relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for
treatment of patients with PMBCL who require urgent cytoreductive therapy.


LOCALLY ADVANCED OR METASTATIC UROTHELIAL CANCER

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment
of adult patients with locally advanced (LA) or metastatic urothelial cancer
(mUC).

KEYTRUDA, as a single agent, is indicated for the treatment of patients with
locally advanced or metastatic urothelial carcinoma who are not eligible for any
platinum-containing chemotherapy.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with
locally advanced or metastatic urothelial carcinoma who have disease progression
during or following platinum-containing chemotherapy or within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.


HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

KEYTRUDA, as a single agent, is indicated for the treatment of patients with
Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive
bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary
tumors who are ineligible for or have elected not to undergo cystectomy.


ADVANCED MSI⁠-⁠H/DMMR CANCERS

KEYTRUDA is indicated for the treatment of adult and pediatric patients with
unresectable or metastatic microsatellite instability-high (MSI⁠-⁠H) or mismatch
repair deficient (dMMR) solid tumors, as determined by an FDA-approved test,
that have progressed following prior treatment and who have no satisfactory
alternative treatment options.


ADVANCED MSI⁠-⁠H/DMMR COLORECTAL CANCER (CRC)

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic MSI⁠-⁠H or dMMR colorectal cancer (CRC) as determined by an
FDA-approved test.


ADVANCED HER2-NEGATIVE GASTRIC OR GEJ ADENOCARCINOMA

KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing
chemotherapy, is indicated for the first-line treatment of adults with locally
advanced unresectable or metastatic HER2-negative gastric or gastroesophageal
junction (GEJ) adenocarcinoma.


ADVANCED ESOPHAGEAL OR GEJ CARCINOMA

KEYTRUDA is indicated for the treatment of patients with locally advanced or
metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter
1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical
resection or definitive chemoradiation either:

 * in combination with platinum- and fluoropyrimidine-based chemotherapy, or
 * as a single agent after one or more prior lines of systemic therapy for
   patients with tumors of squamous cell histology that express programmed death
   ligand 1 (PD⁠-⁠L1) [combined positive score (CPS) ≥10] as determined by an
   FDA-approved test.


ADVANCED CERVICAL CANCER

KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the
treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is
indicated for the treatment of patients with persistent, recurrent, or
metastatic cervical cancer whose tumors express programmed death ligand 1
(PD⁠-⁠L1) [combined positive score (CPS) ≥1] as determined by an FDA-approved
test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with
recurrent or metastatic cervical cancer with disease progression on or after
chemotherapy whose tumors express programmed death ligand 1 (PD⁠-⁠L1) [combined
positive score (CPS) ≥1] as determined by an FDA-approved test.


ADVANCED BILIARY TRACT CANCER (BTC)

KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the
treatment of patients with locally advanced unresectable or metastatic biliary
tract cancer (BTC).


ADVANCED MERKEL CELL CARCINOMA (MCC)

KEYTRUDA is indicated for the treatment of adult and pediatric patients with
recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).


ADJUVANT TREATMENT FOR RCC OR ADVANCED RENAL CELL CARCINOMA (RCC)

KEYTRUDA is indicated for the adjuvant treatment of patients with renal cell
carcinoma (RCC) at intermediate-high or high risk of recurrence following
nephrectomy, or following nephrectomy and resection of metastatic lesions.

KEYTRUDA, in combination with axitinib, is indicated for the first-line
treatment of adult patients with advanced renal cell carcinoma (RCC).


ADVANCED ENDOMETRIAL CARCINOMA

KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA
as a single agent, is indicated for the treatment of adult patients with primary
advanced or recurrent endometrial carcinoma.

KEYTRUDA, as a single agent, is indicated for the treatment of adult patients
with advanced endometrial carcinoma that is MSI⁠-⁠H or dMMR, as determined by an
FDA-approved test, who have disease progression following prior systemic therapy
in any setting and are not candidates for curative surgery or radiation.


ADVANCED CUTANEOUS SQUAMOUS CELL CARCINOMA (CSCC)

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic
cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not
curable by surgery or radiation.


HIGH-RISK EARLY-STAGE OR ADVANCED TRIPLE-NEGATIVE BREAST CANCER (TNBC)

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage
triple-negative breast cancer (TNBC) in combination with chemotherapy as
neoadjuvant treatment, and then continued as a single agent as adjuvant
treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of
patients with locally recurrent unresectable or metastatic triple-negative
breast cancer (TNBC) whose tumors express programmed death ligand 1 (PD⁠-⁠L1)
[combined positive score (CPS) ≥10] as determined by an FDA-approved test.

Selected Safety Information
Severe and Fatal Immune-Mediated Adverse Reactions: KEYTRUDA is a monoclonal
antibody that belongs to a class of drugs that bind to either the programmed
death receptor-1 (PD⁠-⁠1) or the programmed death ligand 1 (PD⁠-⁠L1), blocking
the PD⁠-⁠1/PD⁠-⁠L1 pathway, thereby removing inhibition of the immune response,
potentially breaking peripheral tolerance and inducing immune-mediated adverse
reactions. Immune-mediated adverse reactions, which may be severe or fatal, can
occur in any organ system or tissue, can affect more than one body system
simultaneously, and can occur at any time after starting treatment or after
discontinuation of treatment. Important immune-mediated adverse reactions listed
here may not include all possible severe and fatal immune-mediated adverse
reactions.


SELECTED SAFETY INFORMATION

For KEYTRUDA® (pembrolizumab)
Close


SEVERE AND FATAL IMMUNE-MEDIATED ADVERSE REACTIONS

 * KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind
   to either the programmed death receptor-1 (PD⁠-⁠1) or the programmed death
   ligand 1 (PD⁠-⁠L1), blocking the PD⁠-⁠1/PD⁠-⁠L1 pathway, thereby removing
   inhibition of the immune response, potentially breaking peripheral tolerance
   and inducing immune-mediated adverse reactions. Immune-mediated adverse
   reactions, which may be severe or fatal, can occur in any organ system or
   tissue, can affect more than one body system simultaneously, and can occur at
   any time after starting treatment or after discontinuation of treatment.
   Important immune-mediated adverse reactions listed here may not include all
   possible severe and fatal immune-mediated adverse reactions.

 * Monitor patients closely for symptoms and signs that may be clinical
   manifestations of underlying immune-mediated adverse reactions. Early
   identification and management are essential to ensure safe use of
   anti–PD⁠-⁠1/PD⁠-⁠L1 treatments. Evaluate liver enzymes, creatinine, and
   thyroid function at baseline and periodically during treatment. For patients
   with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood
   cortisol at baseline, prior to surgery, and as clinically indicated. In cases
   of suspected immune-mediated adverse reactions, initiate appropriate workup
   to exclude alternative etiologies, including infection. Institute medical
   management promptly, including specialty consultation as appropriate.

 * Withhold or permanently discontinue KEYTRUDA depending on severity of the
   immune-mediated adverse reaction. In general, if KEYTRUDA requires
   interruption or discontinuation, administer systemic corticosteroid therapy
   (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or
   less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and
   continue to taper over at least 1 month. Consider administration of other
   systemic immunosuppressants in patients whose adverse reactions are not
   controlled with corticosteroid therapy.

IMMUNE-MEDIATED PNEUMONITIS

 * KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in
   patients who have received prior thoracic radiation. Immune-mediated
   pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA,
   including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%)
   reactions. Systemic corticosteroids were required in 67% (63/94) of patients.
   Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and
   withholding in 0.9% (26) of patients. All patients who were withheld
   reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence.
   Pneumonitis resolved in 59% of the 94 patients.

 * Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving
   KEYTRUDA as a single agent, including Grades 3–4 in 2.3% of patients.
   Patients received high-dose corticosteroids for a median duration of 10 days
   (range: 2 days to 53 months). Pneumonitis rates were similar in patients with
   and without prior thoracic radiation. Pneumonitis led to discontinuation of
   KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis,
   42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

 * Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who
   received KEYTRUDA as a single agent for adjuvant treatment of NSCLC,
   including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions.
   Patients received high-dose corticosteroids for a median duration of 10 days
   (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA
   in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54%
   interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

IMMUNE-MEDIATED COLITIS

 * KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea.
   Cytomegalovirus infection/reactivation has been reported in patients with
   corticosteroid-refractory immune-mediated colitis. In cases of
   corticosteroid-refractory colitis, consider repeating infectious workup to
   exclude alternative etiologies. Immune-mediated colitis occurred in 1.7%
   (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3
   (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required
   in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of
   patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15)
   and withholding in 0.5% (13) of patients. All patients who were withheld
   reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence.
   Colitis resolved in 85% of the 48 patients.

HEPATOTOXICITY AND IMMUNE-MEDIATED HEPATITIS

KEYTRUDA AS A SINGLE AGENT

 * KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis
   occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4
   (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic
   corticosteroids were required in 68% (13/19) of patients; additional
   immunosuppressant therapy was required in 11% of patients. Hepatitis led to
   permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9)
   of patients. All patients who were withheld reinitiated KEYTRUDA after
   symptom improvement; of these, none had recurrence. Hepatitis resolved in 79%
   of the 19 patients.

KEYTRUDA WITH AXITINIB

 * KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor
   liver enzymes before initiation of and periodically throughout treatment.
   Consider monitoring more frequently as compared to when the drugs are
   administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA
   and axitinib, and consider administering corticosteroids as needed. With the
   combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine
   aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST)
   (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine
   percent of the patients with increased ALT received systemic corticosteroids.
   In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2–4,
   n=116), ALT resolved to Grades 0–1 in 94%. Among the 92 patients who were
   rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a
   single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed
   in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24
   patients receiving both. All patients with a recurrence of ALT ≥3 ULN
   subsequently recovered from the event.

IMMUNE-MEDIATED ENDOCRINOPATHIES

ADRENAL INSUFFICIENCY

 * KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or
   higher, initiate symptomatic treatment, including hormone replacement as
   clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal
   insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA,
   including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions.
   Systemic corticosteroids were required in 77% (17/22) of patients; of these,
   the majority remained on systemic corticosteroids. Adrenal insufficiency led
   to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3%
   (8) of patients. All patients who were withheld reinitiated KEYTRUDA after
   symptom improvement.

HYPOPHYSITIS

 * KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present
   with acute symptoms associated with mass effect such as headache,
   photophobia, or visual field defects. Hypophysitis can cause hypopituitarism.
   Initiate hormone replacement as indicated. Withhold or permanently
   discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6%
   (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3
   (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required
   in 94% (16/17) of patients; of these, the majority remained on systemic
   corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in
   0.1% (4) and withholding in 0.3% (7) of patients. All patients who were
   withheld reinitiated KEYTRUDA after symptom improvement.

THYROID DISORDERS

 * KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present
   with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism.
   Initiate hormone replacement for hypothyroidism or institute medical
   management of hyperthyroidism as clinically indicated. Withhold or
   permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred
   in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%).
   None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.
 * Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA,
   including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent
   discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of
   patients. All patients who were withheld reinitiated KEYTRUDA after symptom
   improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving
   KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent
   discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of
   patients. All patients who were withheld reinitiated KEYTRUDA after symptom
   improvement. The majority of patients with hypothyroidism required long-term
   thyroid hormone replacement. The incidence of new or worsening hypothyroidism
   was higher in 1185 patients with HNSCC, occurring in 16% of patients
   receiving KEYTRUDA as a single agent or in combination with platinum and FU,
   including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening
   hypothyroidism was higher in 389 adult patients with cHL (17%) receiving
   KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%)
   hypothyroidism. The incidence of new or worsening hyperthyroidism was higher
   in 580 patients with resected NSCLC, occurring in 11% of patients receiving
   KEYTRUDA as a single agent as adjuvant treatment, including Grade 3 (0.2%)
   hyperthyroidism. The incidence of new or worsening hypothyroidism was higher
   in 580 patients with resected NSCLC, occurring in 22% of patients receiving
   KEYTRUDA as a single agent as adjuvant treatment (KEYNOTE⁠-⁠091), including
   Grade 3 (0.3%) hypothyroidism.

TYPE 1 DIABETES MELLITUS (DM), WHICH CAN PRESENT WITH DIABETIC KETOACIDOSIS

 * Monitor patients for hyperglycemia or other signs and symptoms of diabetes.
   Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA
   depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients
   receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and
   withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were
   withheld reinitiated KEYTRUDA after symptom improvement.

IMMUNE-MEDIATED NEPHRITIS WITH RENAL DYSFUNCTION

 * KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis
   occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4
   (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic
   corticosteroids were required in 89% (8/9) of patients. Nephritis led to
   permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3)
   of patients. All patients who were withheld reinitiated KEYTRUDA after
   symptom improvement; of these, none had recurrence. Nephritis resolved in 56%
   of the 9 patients.

IMMUNE-MEDIATED DERMATOLOGIC ADVERSE REACTIONS

 * KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative
   dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia
   and systemic symptoms, and toxic epidermal necrolysis, has occurred
   with anti–PD⁠-⁠1/PD⁠-⁠L1 treatments. Topical emollients and/or topical
   corticosteroids may be adequate to treat mild to moderate nonexfoliative
   rashes. Withhold or permanently discontinue KEYTRUDA depending on severity.
   Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of
   patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%)
   reactions. Systemic corticosteroids were required in 40% (15/38) of patients.
   These reactions led to permanent discontinuation in 0.1% (2) and withholding
   of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld
   reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence.
   The reactions resolved in 79% of the 38 patients.

OTHER IMMUNE-MEDIATED ADVERSE REACTIONS

 * The following clinically significant immune-mediated adverse reactions
   occurred at an incidence of <1% (unless otherwise noted) in patients who
   received KEYTRUDA or were reported with the use of
   other anti–PD⁠-⁠1/PD⁠-⁠L1 treatments. Severe or fatal cases have been
   reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis,
   pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis
   and demyelination, myasthenic syndrome/myasthenia gravis (including
   exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
   neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities
   can occur. Some cases can be associated with retinal detachment. Various
   grades of visual impairment, including blindness, can occur. If uveitis
   occurs in combination with other immune-mediated adverse reactions, consider
   a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with
   systemic steroids to reduce the risk of permanent vision
   loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase
   and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective
   Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae,
   including renal failure), arthritis (1.5%), polymyalgia
   rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic
   anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic
   inflammatory response syndrome, histiocytic necrotizing lymphadenitis
   (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid
   organ transplant rejection, other transplant (including corneal graft)
   rejection.


INFUSION-RELATED REACTIONS

 * KEYTRUDA can cause severe or life-threatening infusion-related reactions,
   including hypersensitivity and anaphylaxis, which have been reported in 0.2%
   of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of
   infusion-related reactions. Interrupt or slow the rate of infusion for Grade
   1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and
   permanently discontinue KEYTRUDA.


COMPLICATIONS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)

 * Fatal and other serious complications can occur in patients who receive
   allogeneic HSCT before or after anti–PD⁠-⁠1/PD⁠-⁠L1 treatments.
   Transplant-related complications include hyperacute graft-versus-host disease
   (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced
   intensity conditioning, and steroid-requiring febrile syndrome (without an
   identified infectious cause). These complications may occur despite
   intervening therapy between anti–PD⁠-⁠1/PD⁠-⁠L1 treatments and allogeneic
   HSCT. Follow patients closely for evidence of these complications and
   intervene promptly. Consider the benefit vs risks of
   using anti–PD⁠-⁠1/PD⁠-⁠L1 treatments prior to or after an allogeneic HSCT.


INCREASED MORTALITY IN PATIENTS WITH MULTIPLE MYELOMA

 * In trials in patients with multiple myeloma, the addition of KEYTRUDA to a
   thalidomide analogue plus dexamethasone resulted in increased mortality.
   Treatment of these patients with an anti–PD⁠-⁠1/PD⁠-⁠L1 treatment in this
   combination is not recommended outside of controlled trials.


EMBRYOFETAL TOXICITY

 * Based on its mechanism of action, KEYTRUDA can cause fetal harm when
   administered to a pregnant woman. Advise women of this potential risk. In
   females of reproductive potential, verify pregnancy status prior to
   initiating KEYTRUDA and advise them to use effective contraception during
   treatment and for 4 months after the last dose.


ADVERSE REACTIONS

 * In KEYNOTE⁠-⁠006, KEYTRUDA was discontinued due to adverse reactions in 9% of
   555 patients with advanced melanoma; adverse reactions leading to permanent
   discontinuation in more than one patient were colitis (1.4%), autoimmune
   hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
   cardiac failure (0.4%). The most common adverse reactions (≥20%) with
   KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

 * In KEYNOTE⁠-⁠054, when KEYTRUDA was administered as a single agent to
   patients with stage III melanoma, KEYTRUDA was permanently discontinued due
   to adverse reactions in 14% of 509 patients; the most common (≥1%) were
   pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse
   reactions occurred in 25% of patients receiving KEYTRUDA. The most common
   adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE⁠-⁠716,
   when KEYTRUDA was administered as a single agent to patients with stage IIB
   or IIC melanoma, adverse reactions occurring in patients with stage IIB or
   IIC melanoma were similar to those occurring in 1011 patients with stage III
   melanoma from KEYNOTE⁠-⁠054.

 * In KEYNOTE⁠-⁠189, when KEYTRUDA was administered with pemetrexed and platinum
   chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due
   to adverse reactions in 20% of 405 patients. The most common adverse
   reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis
   (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%)
   with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea
   (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%),
   dyspnea (21%), and pyrexia (20%).

 * In KEYNOTE⁠-⁠407, when KEYTRUDA was administered with carboplatin and either
   paclitaxel or paclitaxel protein‑bound in metastatic squamous NSCLC, KEYTRUDA
   was discontinued due to adverse reactions in 15% of 101 patients. The most
   frequent serious adverse reactions reported in at least 2% of patients were
   febrile neutropenia, pneumonia, and urinary tract infection. Adverse
   reactions observed in KEYNOTE⁠-⁠407 were similar to those observed in
   KEYNOTE⁠-⁠189 with the exception that increased incidences of alopecia (47%
   vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA
   and chemotherapy arm compared to the placebo and chemotherapy arm in
   KEYNOTE⁠-⁠407.

 * In KEYNOTE⁠-⁠042, KEYTRUDA was discontinued due to adverse reactions in 19%
   of 636 patients with advanced NSCLC; the most common were pneumonitis (3%),
   death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent
   serious adverse reactions reported in at least 2% of patients were pneumonia
   (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion
   (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

 * In KEYNOTE⁠-⁠010, KEYTRUDA monotherapy was discontinued due to adverse
   reactions in 8% of 682 patients with metastatic NSCLC; the most common was
   pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased
   appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

 * In KEYNOTE⁠-⁠671, adverse reactions occurring in patients with resectable
   NSCLC receiving KEYTRUDA in combination with platinum-containing
   chemotherapy, given as neoadjuvant treatment and continued as single-agent
   adjuvant treatment, were generally similar to those occurring in patients in
   other clinical trials across tumor types receiving KEYTRUDA in combination
   with chemotherapy.

 * The most common adverse reactions (reported in ≥20%) in patients receiving
   KEYTRUDA in combination with chemotherapy were fatigue/asthenia, nausea,
   constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea,
   pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis,
   headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia,
   palmar-plantar erythrodysesthesia, urinary tract infection, and
   hypothyroidism.

 * In the neoadjuvant phase of KEYNOTE⁠-⁠671, when KEYTRUDA was administered in
   combination with platinum-containing chemotherapy as neoadjuvant treatment,
   serious adverse reactions occurred in 34% of 396 patients. The most frequent
   (≥2%) serious adverse reactions were pneumonia (4.8%), venous thromboembolism
   (3.3%), and anemia (2%). Fatal adverse reactions occurred in 1.3% of
   patients, including death due to unknown cause (0.8%), sepsis (0.3%), and
   immune-mediated lung disease (0.3%). Permanent discontinuation of any study
   drug due to an adverse reaction occurred in 18% of patients who received
   KEYTRUDA in combination with platinum-containing chemotherapy; the most
   frequent adverse reactions (≥1%) that led to permanent discontinuation of any
   study drug were acute kidney injury (1.8%), interstitial lung disease (1.8%),
   anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%).

 * Of the KEYTRUDA-treated patients who received neoadjuvant treatment, 6% of
   396 patients did not receive surgery due to adverse reactions. The most
   frequent (≥1%) adverse reaction that led to cancellation of surgery in the
   KEYTRUDA arm was interstitial lung disease (1%).

 * In the adjuvant phase of KEYNOTE⁠-⁠671, when KEYTRUDA was administered as a
   single agent as adjuvant treatment, serious adverse reactions occurred in 14%
   of 290 patients. The most frequent serious adverse reaction was pneumonia
   (3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred.
   Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in
   12% of patients who received KEYTRUDA as a single agent, given as adjuvant
   treatment; the most frequent adverse reactions (≥1%) that led to permanent
   discontinuation of KEYTRUDA were diarrhea (1.7%), interstitial lung disease
   (1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain
   (1%).

 * Adverse reactions observed in KEYNOTE⁠-⁠091 were generally similar to those
   occurring in other patients with NSCLC receiving KEYTRUDA as a single agent,
   with the exception of hypothyroidism (22%), hyperthyroidism (11%), and
   pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.

 * In KEYNOTE⁠-⁠048, KEYTRUDA monotherapy was discontinued due to adverse events
   in 12% of 300 patients with HNSCC; the most common adverse reactions leading
   to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The
   most common adverse reactions (≥20%) were fatigue (33%), constipation (20%),
   and rash (20%).

 * In KEYNOTE⁠-⁠048, when KEYTRUDA was administered in combination with platinum
   (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due
   to adverse reactions in 16% of 276 patients with HNSCC. The most common
   adverse reactions resulting in permanent discontinuation of KEYTRUDA were
   pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most
   common adverse reactions (≥20%) were nausea (51%), fatigue (49%),
   constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea
   (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

 * In KEYNOTE⁠-⁠012, KEYTRUDA was discontinued due to adverse reactions in 17%
   of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of
   patients. The most frequent serious adverse reactions reported in at least 2%
   of patients were pneumonia, dyspnea, confusional state, vomiting, pleural
   effusion, and respiratory failure. The most common adverse reactions (≥20%)
   were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in
   patients with HNSCC were generally similar to those occurring in patients
   with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the
   exception of increased incidences of facial edema and new or worsening
   hypothyroidism.

 * In KEYNOTE⁠-⁠204, KEYTRUDA was discontinued due to adverse reactions in 14%
   of 148 patients with cHL. Serious adverse reactions occurred in 30% of
   patients receiving KEYTRUDA; those ≥1% were pneumonitis, pneumonia, pyrexia,
   myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three
   patients died from causes other than disease progression: 2 from
   complications after allogeneic HSCT and 1 from unknown cause. The most common
   adverse reactions (≥20%) were upper respiratory tract infection (41%),
   musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash, and
   cough (20% each).

 * In KEYNOTE⁠-⁠087, KEYTRUDA was discontinued due to adverse reactions in 5% of
   210 patients with cHL. Serious adverse reactions occurred in 16% of patients;
   those ≥1% were pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes
   zoster. Two patients died from causes other than disease progression: 1 from
   GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most
   common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough
   (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

 * In KEYNOTE⁠-⁠170, KEYTRUDA was discontinued due to adverse reactions in 8% of
   53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients
   and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction
   (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients
   died within 30 days of start of treatment. The most common adverse reactions
   (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and
   pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

 * In KEYNOTE⁠-⁠A39, when KEYTRUDA was administered in combination with
   enfortumab vedotin to patients with locally advanced or metastatic urothelial
   cancer (n=440), fatal adverse reactions occurred in 3.9% of patients,
   including acute respiratory failure (0.7%), pneumonia (0.5%), and
   pneumonitis/ILD (0.2%). Serious adverse reactions occurred in 50% of patients
   receiving KEYTRUDA in combination with enfortumab vedotin; the serious
   adverse reactions in ≥2% of patients were rash (6%), acute kidney injury
   (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea
   (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Permanent
   discontinuation of KEYTRUDA occurred in 27% of patients. The most common
   adverse reactions (≥2%) resulting in permanent discontinuation of KEYTRUDA
   were pneumonitis/ILD (4.8%) and rash (3.4%). The most common adverse
   reactions (≥20%) occurring in patients treated with KEYTRUDA in combination
   with enfortumab vedotin were rash (68%), peripheral neuropathy (67%), fatigue
   (51%), pruritus (41%), diarrhea (38%), alopecia (35%), weight loss (33%),
   decreased appetite (33%), nausea (26%), constipation (26%), dry eye (24%),
   dysgeusia (21%), and urinary tract infection (21%).

 * In KEYNOTE⁠-⁠052, KEYTRUDA was discontinued due to adverse reactions in 11%
   of 370 patients with locally advanced or metastatic urothelial carcinoma.
   Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary
   tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.
   The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal
   pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and
   diarrhea (20%).

 * In KEYNOTE⁠-⁠045, KEYTRUDA was discontinued due to adverse reactions in 8% of
   266 patients with locally advanced or metastatic urothelial carcinoma. The
   most common adverse reaction resulting in permanent discontinuation of
   KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of
   KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia,
   anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients
   who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%),
   pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

 * In KEYNOTE⁠-⁠057, KEYTRUDA was discontinued due to adverse reactions in 11%
   of 148 patients with high-risk NMIBC. The most common adverse reaction
   resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%).
   Serious adverse reactions occurred in 28% of patients; those ≥2% were
   pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%),
   sepsis (2%), and urinary tract infection (2%). The most common adverse
   reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

 * Adverse reactions occurring in patients with MSI⁠-⁠H or dMMR CRC were similar
   to those occurring in patients with melanoma or NSCLC who received KEYTRUDA
   as a monotherapy.

 * In KEYNOTE⁠-⁠158 and KEYNOTE⁠-⁠164, adverse reactions occurring in patients
   with MSI⁠-⁠H or dMMR cancer were similar to those occurring in patients with
   other solid tumors who received KEYTRUDA as a single agent.

 * In KEYNOTE⁠-⁠859, when KEYTRUDA was administered in combination with
   fluoropyrimidine- and platinum-containing chemotherapy, serious adverse
   reactions occurred in 45% of 785 patients. Serious adverse reactions in >2%
   of patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%),
   and vomiting (2.4%). Fatal adverse reactions occurred in 8% of patients who
   received KEYTRUDA, including infection (2.3%) and thromboembolism (1.3%).
   KEYTRUDA was permanently discontinued due to adverse reactions in 15% of
   patients. The most common adverse reactions resulting in permanent
   discontinuation of KEYTRUDA (≥1%) were infections (1.8%) and diarrhea (1.0%).
   The most common adverse reactions (reported in ≥20%) in patients receiving
   KEYTRUDA in combination with chemotherapy were peripheral neuropathy (47%),
   nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased
   appetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia
   syndrome (25%), constipation (22%), and weight loss (20%).

 * In KEYNOTE⁠-⁠590, when KEYTRUDA was administered with cisplatin and
   fluorouracil to patients with metastatic or locally advanced esophageal or
   GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who
   were not candidates for surgical resection or definitive chemoradiation,
   KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients.
   The most common adverse reactions resulting in permanent discontinuation of
   KEYTRUDA (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and
   pneumonia (1.1%). The most common adverse reactions (≥20%) with KEYTRUDA in
   combination with chemotherapy were nausea (67%), fatigue (57%), decreased
   appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%),
   stomatitis (27%), and weight loss (24%).

 * Adverse reactions occurring in patients with esophageal cancer who received
   KEYTRUDA as a monotherapy were similar to those occurring in patients with
   melanoma or NSCLC who received KEYTRUDA as a monotherapy.

 * In KEYNOTE⁠-⁠A18, when KEYTRUDA was administered with CRT (cisplatin plus
   external beam radiation therapy [EBRT] followed by brachytherapy [BT]) to
   patients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse
   reactions occurred in 1.4% of 292 patients, including 1 case each (0.3%) of
   large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage.
   Serious adverse reactions occurred in 30% of patients; those ≥1% included
   urinary tract infection (2.7%), urosepsis (1.4%), and sepsis (1%). KEYTRUDA
   was discontinued for adverse reactions in 7% of patients. The most common
   adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea
   (1%). For patients treated with KEYTRUDA in combination with CRT, the most
   common adverse reactions (≥10%) were nausea (56%), diarrhea (50%), vomiting
   (33%), urinary tract infection (32%), fatigue (26%), hypothyroidism (20%),
   constipation (18%), decreased appetite and weight loss (17% each), abdominal
   pain and pyrexia (12% each), hyperthyroidism, dysuria, rash (11% each), and
   pelvic pain (10%).

 * In KEYNOTE⁠-⁠826, when KEYTRUDA was administered in combination with
   paclitaxel and cisplatin or paclitaxel and carboplatin, with or without
   bevacizumab (n=307), to patients with persistent, recurrent, or first-line
   metastatic cervical cancer regardless of tumor PD⁠-⁠L1 expression who had not
   been treated with chemotherapy except when used concurrently as a
   radio-sensitizing agent, fatal adverse reactions occurred in 4.6% of
   patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to
   unknown causes, and 1 case each of acute myocardial infarction, autoimmune
   encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with
   perioperative pulmonary embolus, intestinal perforation, and pelvic
   infection. Serious adverse reactions occurred in 50% of patients receiving
   KEYTRUDA in combination with chemotherapy with or without bevacizumab; those
   ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia
   (4.6%), and acute kidney injury and sepsis (3.3% each).

 * KEYTRUDA was discontinued in 15% of patients due to adverse reactions. The
   most common adverse reaction resulting in permanent discontinuation (≥1%) was
   colitis (1%).

 * For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196),
   the most common adverse reactions (≥20%) were peripheral neuropathy (62%),
   alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia
   (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each),
   constipation and arthralgia (31% each), vomiting (30%), urinary tract
   infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and
   decreased appetite (21%).

 * For patients treated with KEYTRUDA in combination with chemotherapy with or
   without bevacizumab, the most common adverse reactions (≥20%) were peripheral
   neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea
   (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and
   urinary tract infection (24% each), and rash (22%).

 * In KEYNOTE⁠-⁠158, KEYTRUDA was discontinued due to adverse reactions in 8% of
   98 patients with previously treated recurrent or metastatic cervical cancer.
   Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the
   most frequent included anemia (7%), fistula, hemorrhage, and infections
   [except urinary tract infections] (4.1% each). The most common adverse
   reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea
   (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

 * In KEYNOTE⁠-⁠966, when KEYTRUDA was administered in combination with
   gemcitabine and cisplatin, KEYTRUDA was discontinued for adverse reactions in
   15% of 529 patients with locally advanced unresectable or metastatic biliary
   tract cancer. The most common adverse reaction resulting in permanent
   discontinuation of KEYTRUDA (≥1%) was pneumonitis (1.3%). Adverse reactions
   leading to the interruption of KEYTRUDA occurred in 55% of patients. The most
   common adverse reactions or laboratory abnormalities leading to interruption
   of KEYTRUDA (≥2%) were decreased neutrophil count (18%), decreased platelet
   count (10%), anemia (6%), decreased white blood cell count (4%), pyrexia
   (3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased
   AST (2.5%), and biliary obstruction (2.3%).

 * In KEYNOTE⁠-⁠017 and KEYNOTE⁠-⁠913, adverse reactions occurring in patients
   with MCC (n=105) were generally similar to those occurring in patients with
   melanoma or NSCLC who received KEYTRUDA as a single agent.

 * In KEYNOTE⁠-⁠426, when KEYTRUDA was administered in combination with
   axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious
   adverse reactions occurred in 40% of patients, the most frequent (≥1%) were
   hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration
   (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse
   reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only
   (13%), and the combination (8%); the most common were hepatotoxicity (13%),
   diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular
   accident (1.2%). The most common adverse reactions (≥20%) were diarrhea
   (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%),
   hypothyroidism (35%), decreased appetite (30%), palmar-plantar
   erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation
   (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

 * In KEYNOTE⁠-⁠564, when KEYTRUDA was administered as a single agent for the
   adjuvant treatment of renal cell carcinoma, serious adverse reactions
   occurred in 20% of patients receiving KEYTRUDA; the serious adverse reactions
   (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis,
   and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2%
   including 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse
   reactions occurred in 21% of 488 patients; the most common (≥1%) were
   increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most
   common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue
   (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

 * In KEYNOTE⁠-⁠868, when KEYTRUDA was administered in combination with
   chemotherapy (paclitaxel and carboplatin) to patients with advanced or
   recurrent endometrial carcinoma (n=759), serious adverse reactions occurred
   in 35% of patients receiving KEYTRUDA in combination with chemotherapy,
   compared to 19% of patients receiving placebo in combination with
   chemotherapy. Fatal adverse reactions occurred in 1.6% of patients receiving
   KEYTRUDA in combination with chemotherapy, including COVID-19 (0.5%) and
   cardiac arrest (0.3%). KEYTRUDA was discontinued for an adverse reaction in
   14% of patients. Adverse reactions occurring in patients treated with
   KEYTRUDA and chemotherapy were generally similar to those observed with
   KEYTRUDA alone or chemotherapy alone, with the exception of rash (33% all
   Grades; 2.9% Grades 3-4).

 * Adverse reactions occurring in patients with MSI⁠-⁠H or dMMR endometrial
   carcinoma who received KEYTRUDA as a single agent were similar to those
   occurring in patients with melanoma or NSCLC who received KEYTRUDA as a
   single agent.

 * Adverse reactions occurring in patients with recurrent or metastatic cSCC or
   locally advanced cSCC were similar to those occurring in patients with
   melanoma or NSCLC who received KEYTRUDA as a monotherapy.

 * In KEYNOTE⁠-⁠522, when KEYTRUDA was administered with neoadjuvant
   chemotherapy (carboplatin and paclitaxel followed by doxorubicin or
   epirubicin and cyclophosphamide) followed by surgery and continued adjuvant
   treatment with KEYTRUDA as a single agent (n=778) to patients with newly
   diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse
   reactions occurred in 0.9% of patients, including 1 each of adrenal crisis,
   autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary
   embolism, and sepsis in association with multiple organ dysfunction syndrome
   and myocardial infarction. Serious adverse reactions occurred in 44% of
   patients receiving KEYTRUDA; those ≥2% were febrile neutropenia (15%),
   pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). KEYTRUDA was
   discontinued in 20% of patients due to adverse reactions. The most common
   reactions (≥1%) resulting in permanent discontinuation were increased ALT
   (2.7%), increased AST (1.5%), and rash (1%). The most common adverse
   reactions (≥20%) in patients receiving KEYTRUDA were fatigue (70%), nausea
   (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and
   peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache
   (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%),
   decreased appetite (23%), insomnia (21%), and myalgia (20%).

 * In KEYNOTE⁠-⁠355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel
   protein⁠-⁠bound, or gemcitabine and carboplatin) were administered to
   patients with locally recurrent unresectable or metastatic TNBC who had not
   been previously treated with chemotherapy in the metastatic setting (n=596),
   fatal adverse reactions occurred in 2.5% of patients, including
   cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse
   reactions occurred in 30% of patients receiving KEYTRUDA in combination with
   chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia
   (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of
   patients due to adverse reactions. The most common reactions resulting in
   permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST
   (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in
   patients receiving KEYTRUDA in combination with chemotherapy were fatigue
   (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each),
   vomiting and rash (26% each), cough (23%), decreased appetite (21%), and
   headache (20%).


LACTATION

 * Because of the potential for serious adverse reactions in breastfed children,
   advise women not to breastfeed during treatment and for 4 months after the
   last dose.


PEDIATRIC USE

 * In KEYNOTE⁠-⁠051, 173 pediatric patients (65 pediatric patients aged 6 months
   to younger than 12 years and 108 pediatric patients aged 12 years to 17
   years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration
   of exposure was 2.1 months (range: 1 day to 25 months).

 * Adverse reactions that occurred at a ≥10% higher rate in pediatric patients
   when compared to adults were pyrexia (33%), leukopenia (31%), vomiting (29%),
   neutropenia (28%), headache (25%), abdominal pain (23%), thrombocytopenia
   (22%), Grade 3 anemia (17%), decreased lymphocyte count (13%), and decreased
   white blood cell count (11%).

Geriatric Use
 * Of the 564 patients with locally advanced or metastatic urothelial cancer
   treated with KEYTRUDA in combination with enfortumab vedotin, 44% (n=247)
   were 65-74 years and 26% (n=144) were 75 years or older. No overall
   differences in safety or effectiveness were observed between patients 65
   years of age or older and younger patients. Patients 75 years of age or older
   treated with KEYTRUDA in combination with enfortumab vedotin experienced a
   higher incidence of fatal adverse reactions than younger patients. The
   incidence of fatal adverse reactions was 4% in patients younger than 75 and
   7% in patients 75 years or older.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; BT =
brachytherapy; BTC = biliary tract cancer; cHL = classical Hodgkin lymphoma; CRC
= colorectal cancer; CRT = chemoradiotherapy; cSCC = cutaneous squamous cell
carcinoma; dMMR = mismatch repair deficient; EBRT = external beam radiation
therapy; FIGO = International Federation of Gynecology and Obstetrics; FU =
fluorouracil; GEJ = gastroesophageal junction; HER2 = human epidermal growth
factor receptor 2; HNSCC = head and neck squamous cell carcinoma; ILD =
interstitial lung disease; MCC = Merkel cell carcinoma; MSI⁠-⁠H = microsatellite
instability-high; NMIBC = non-muscle invasive bladder cancer; NSCLC = non–small
cell lung cancer; PMBCL = primary mediastinal large B-cell lymphoma; TNBC =
triple-negative breast cancer.

BEFORE PRESCRIBING KEYTRUDA® (PEMBROLIZUMAB), PLEASE READ THE ACCOMPANYING
PRESCRIBING INFORMATION. THE MEDICATION GUIDE ALSO IS AVAILABLE.




This Site Uses Cookies and Your Privacy Choice Is Important to Us. Choose
Customize My Settings to make your privacy choices. Choose Accept All Cookies to
accept third-party cookies.See our Privacy Policy
Customize My Settings Accept All Cookies



Skip to End of Chat

Please type a message to continue.
Send
0/200
To report a side effect or product quality complaint, call 85‑KEYTRUDA.
Need Help?

Your session will expire in two minutes. Do you wish to continue?
YesNo
Are you sure? Clicking “Yes” will close the entire chat window.
YesNo