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INDICATIONS

Melanoma

KEYTRUDA is indicated for the treatment of adult and pediatric (12 years and older) 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.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) negative for EGFR or ALK genomic tumour aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of patients with metastatic squamous NSCLC .
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 [Tumor Proportion Score (TPS) ≥50%)] as determined by a validated test. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on or after platinum-containing chemotherapy and an approved therapy for these aberrations prior to receiving KEYTRUDA .
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced NSCLC whose tumors express PD-L1 as determined by a validated test, with disease progression on or after platinum containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on approved therapy for these aberrations prior to receiving KEYTRUDA .
KEYTRUDA, in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment, is indicated for the treatment of NSCLC at high risk of recurrence in adults (for selection criteria, see section 14 CLINICAL STUDIES of the Prescribing Information).
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

Malignant Pleural Mesothelioma

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adults with unresectable non-epithelioid malignant pleural mesothelioma.

Head and Neck Cancer

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 HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by a validated test.
KEYTRUDA 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.

Classical Hodgkin Lymphoma

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 cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal large B-Cell Lymphoma

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. Limitation of Use: KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Cancer

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS ≥10) as determined by a validated test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
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
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

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient: solid tumors that have progressed following prior systemic treatment and who have no satisfactory alternative treatment options, or colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Limitation of Use: The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer (CRC)

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastro- esophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 with a CPS≥1 as determined by a validated test.
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 whose tumors express PD-L1 with a CPS ≥ 1, as determined by a validated test.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (Siewert type I) carcinoma that is not amenable to surgical resection or definitive chemoradiation in combination with platinum- and fluoropyrimidine-based chemotherapy.
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS≥10) as determined by a validated test, with disease progression after one or more prior lines of systemic therapy.

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 PDL1 (CPS ≥1) as determined by a validated 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 PD-L1 (CPS ≥1) as determined by a validated test.

Biliary Tract Cancer

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

Merkel Cell Carcinoma

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

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment of adult patients with advanced RCC.
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma

KEYTRUDA, in combination with carboplatin and paclitaxel, followed by Keytruda as a single agent, for the treatment of adult patients with primary advanced or recurrent pMMR endometrial carcinoma at least 12 months from prior adjuvant chemotherapy, and dMMR endometrial carcinoma regardless of prior adjuvant treatment.
KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy and who are not candidates for curative surgery or radiation.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by a validated test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Limitations of Use: The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

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.

Triple Negative Breast Cancer

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 TNBC whose tumors express PD-L1 (CPS ≥10) as determined by a validated test.

DOSAGE AND ADMINISTRATION

Patient Selection for Single Agent Treatment

Select patients for treatment with KEYTRUDA as a single agent based on the presence of positive PD-L1 expression in:

-Metastatic NSCLC
-First-line treatment of metastatic or unresectable, recurrent HNSCC
-Metastatic urothelial carcinoma
-Previously treated recurrent locally advanced or metastatic Esophageal Cancer
-Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy

For the MSI-H/dMMR indications, select patients for treatment with KEYTRUDA as a single agent based on MSI-H/dMMR status in tumor specimens. For the TMB-H indication, select patients for treatment with KEYTRUDA as a single agent based on TMB-H status in tumor specimens.

Because the effect of prior chemotherapy on test results for tumor mutation burden (TMB-H), MSI-H, or dMMR in patients with high-grade gliomas is unclear, it is recommended to test for these markers in the primary tumor specimens obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas.

Patient Selection for Combination Therapy

For use of KEYTRUDA in combination with chemotherapy, select patients based on the presence of positive PD L1 expression (CPS ≥1) in locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
For use of KEYTRUDA in combination with chemotherapy, with or without bevacizumab, select patients based on the presence of positive PD L1 expression in persistent, recurrent, or metastatic cervical cancer.
For use of KEYTRUDA in combination with chemotherapy, select patients based on the presence of positive PD-L1 expression in locally recurrent unresectable or metastatic TNBC

Recommended Dosage for Melanoma:

The recommended dose of KEYTRUDA in patients with unresectable or metastatic melanoma is 200 mg or 2 mg/kg, according to treating physician's discretion, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
The recommended dose of KEYTRUDA for the treatment of pediatric patients (12 years and older) with unresectable or metastatic melanoma is 2 mg/kg (up to a maximum of 200 mg) administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence or unacceptable toxicity.
The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months.
The recommended dose of KEYTRUDA for the adjuvant treatment of pediatric patients (12 years and older) with melanoma is 2 mg/kg (up to a maximum of 200 mg) administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or up to 12 months.

Recommended Dosage for NSCLC:

For first-line treatment:
The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.
For second-line or greater treatment:
The recommended dose of KEYTRUDA is 200 mg or 2 mg/kg, according to treating physician's discretion, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
For adjuvant treatment:
The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with NSCLC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months.
For neoadjuvant/adjuvant treatment:
The recommended dose of KEYTRUDA for the neoadjuvant treatment of adult patients with resectable NSCLC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with chemotherapy for 12 weeks (4 doses of 200 mg every 3 weeks) or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent after surgery for 39 weeks (13 doses of 200 mg every 3 weeks) or until disease recurrence or unacceptable toxicity.

Recommended Dosage for MPM:

The recommended dose of KEYTRUDA in patients with MPM is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity or up to 24 months.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for HNSCC:

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for cHL

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for PMBCL

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for Urothelial Cancer

The recommended dose of KEYTRUDA in patients with locally advanced or metastatic urothelial cancer is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with enfortumab vedotin, administer KEYTRUDA after enfortumab vedotin when given on the same day. Refer to the Prescribing Information for enfortumab vedotin administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
The recommended dose of KEYTRUDA in patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until persistent or recurrent high-risk NMIBC, disease progression or unacceptable toxicity, or up to 24 months.

Recommended Dosage for MSI-H/dMMR Cancer

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in children is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for MSI-H/dMMR Colorectal Cancer (CRC)

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.

Recommended Dosage for Gastric Cancer

The recommended dose of KEYTRUDA in adult is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with trastuzumab and chemotherapy, administer KEYTRUDA prior to trastuzumab and chemotherapy when given on the same day. Refer to the prescribing information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for Esophageal Cancer

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months. When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day.
Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.

Recommended Dosage for Cervical Cancer

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or for KEYTRUDA up to 24 months.
The recommended dose of KEYTRUDA in adults in combination with chemoradiotherapy is 200 mg every 3 weeks for 5 or 6 cycles followed by 400 mg every 6 weeks, administered as an intravenous infusion over 30 minutes until disease progression, unacceptable toxicity, or for KEYTRUDA up to 24 months.
For combination therapy, administer KEYTRUDA prior to chemoradiotherapy or prior to chemotherapy with or without bevacizumab when given on the same day. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for Biliary Tract Cancer

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for MCC

The recommended dose of KEYTRUDA in adults is 200 mg or 2 mg/kg, according to treating physician's discretion, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for RCC

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg axitinib orally twice daily or in combination with lenvatinib 20 mg orally once daily until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months.
When axitinib is used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with RCC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months.

Recommended Dosage for Endometrial Carcinoma

The recommended dose of KEYTRUDA in adults in combination with chemotherapy is 200 mg every 3 weeks administered as an intravenous infusion over 30 minutes until disease progression, unacceptable toxicity, or for up to 6 cycles.
When KEYTRUDA is administrated alone for maintenance therapy, the recommended dose is 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes until disease progression, unacceptable toxicity, or for up to 24 months.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with lenvatinib 20 mg orally once daily until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for TMB-H Cancer

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
The recommended dose of KEYTRUDA in pediatric is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months.

Recommended Dosage for cSCC

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
The recommended dose of KEYTRUDA in patients with locally recurrent unresectable or metastatic TNBC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.

Recommended Dosage for TNBC

The recommended dose of KEYTRUDA in adult patients with high-risk early-stage TNBC for neoadjuvant treatment is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with chemotherapy for 24 weeks (8 doses of 200mg every 3 weeks) or until disease progression or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent for up to 27 weeks (9 doses of 200 mg every 3 weeks) or until disease recurrence or unacceptable toxicity.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate. Patients who experience disease progression or unacceptable toxicity related to KEYTRUDA with neoadjuvant treatment in combination with chemotherapy should not receive adjuvant single agent KEYTRUDA.

The recommended dose of KEYTRUDA in patients with locally recurrent unresectable or metastatic TNBC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.

Dose Modifications

No dose reduction for KEYTRUDA is recommended. In general, withhold KEYTRUDA for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue KEYTRUDA for Life-threatening (Grade 4) immune- mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids.
Dosage modifications for KEYTRUDA for adverse reactions that require management different from these general guidelines are summarized in Table 1 & Table 2 of Dosage Modifications section in the full Prescribing Information (PI).
Recommended Dose Modifications for Adverse Reactions for KEYTRUDA in Combination with Lenvatinib
When administering KEYTRUDA in combination with Lenvatinib, modify the dosage of one or both drugs. Withhold or discontinue KEYTRUDA as shown in Table 1 of Dosage Modifications (section 2.20) in the full PI. Refer to Lenvatinib prescribing information for additional dose modification information.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients listed in section 11 of the Prescribing Information.
DRUG INTERACTION: No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA.

WARNINGS AND PRECAUTIONS:

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 PD-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. Important immune-mediated adverse reactions listed under WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. 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. 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 immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence of pneumonitis 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%) adverse reactions. Systemic corticosteroids were required in 67% (63/94) of patients with pneumonitis.
Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) of patients and withholding of KEYTRUDA in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence of pneumonitis. Pneumonitis resolved in 59% of the 94 patients.
In clinical studies enrolling 389 adult patients with cHL who received KEYTRUDA as a single agent, pneumonitis occurred in 31 (8%) patients, including Grades 3-4 pneumonitis 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 21 (5.4%) patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.
In a clinical study enrolling 580 adult patients with resected NSCLC (KEYNOTE-091) who received KEYTRUDA as a single agent for adjuvant treatment, pneumonitis occurred in 41 (7%) patients, 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 (CMV) 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%) adverse reactions. Systemic corticosteroids were required in 69% (33/48) of patients with colitis. Additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) of patients and withholding of KEYTRUDA in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence of colitis. Colitis resolved in 85% of the 48 patients.

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%) adverse reactions. Systemic corticosteroids were required in 68% (13/19) of patients with hepatitis. Eleven percent of these patients required additional immunosuppressant therapy. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) of patients and withholding of KEYTRUDA in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence of hepatitis. Hepatitis resolved in 79% of the 19 patients.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, 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%) adverse reactions. Systemic corticosteroids were required in 77% (17/22) of patients with adrenal insufficiency; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) of patients and withholding of KEYTRUDA 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%) adverse reactions. Systemic corticosteroids were required in 94% (16/17) of patients with hypophysitis; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) of patients and withholding of KEYTRUDA in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Keytruda SSI

Short description

INDICATIONS

Melanoma

KEYTRUDA is indicated for the treatment of adult and pediatric (12 years and older) 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.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) negative for EGFR or ALK genomic tumour aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of patients with metastatic squamous NSCLC .
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 [Tumor Proportion Score (TPS) ≥50%)] as determined by a validated test. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on or after platinum-containing chemotherapy and an approved therapy for these aberrations prior to receiving KEYTRUDA .
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced NSCLC whose tumors express PD-L1 as determined by a validated test, with disease progression on or after platinum containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on approved therapy for these aberrations prior to receiving KEYTRUDA .
KEYTRUDA, in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment, is indicated for the treatment of NSCLC at high risk of recurrence in adults (for selection criteria, see section 14 CLINICAL STUDIES of the Prescribing Information).
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

Malignant Pleural Mesothelioma

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adults with unresectable non-epithelioid malignant pleural mesothelioma.

Head and Neck Cancer

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 HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by a validated test.
KEYTRUDA 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.

Classical Hodgkin Lymphoma

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 cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal large B-Cell Lymphoma

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. Limitation of Use: KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Cancer

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS ≥10) as determined by a validated test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
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
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

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient: solid tumors that have progressed following prior systemic treatment and who have no satisfactory alternative treatment options, or colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Limitation of Use: The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer (CRC)

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastro- esophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 with a CPS≥1 as determined by a validated test.
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 whose tumors express PD-L1 with a CPS ≥ 1, as determined by a validated test.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (Siewert type I) carcinoma that is not amenable to surgical resection or definitive chemoradiation in combination with platinum- and fluoropyrimidine-based chemotherapy.
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS≥10) as determined by a validated test, with disease progression after one or more prior lines of systemic therapy.

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 PDL1 (CPS ≥1) as determined by a validated 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 PD-L1 (CPS ≥1) as determined by a validated test.

Biliary Tract Cancer

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

Merkel Cell Carcinoma

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

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment of adult patients with advanced RCC.
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma

KEYTRUDA, in combination with carboplatin and paclitaxel, followed by Keytruda as a single agent, for the treatment of adult patients with primary advanced or recurrent pMMR endometrial carcinoma at least 12 months from prior adjuvant chemotherapy, and dMMR endometrial carcinoma regardless of prior adjuvant treatment.
KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy and who are not candidates for curative surgery or radiation.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by a validated test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Limitations of Use: The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

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.

Triple Negative Breast Cancer

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 TNBC whose tumors express PD-L1 (CPS ≥10) as determined by a validated test.

DOSAGE AND ADMINISTRATION

Patient Selection for Single Agent Treatment

Select patients for treatment with KEYTRUDA as a single agent based on the presence of positive PD-L1 expression in:

-Metastatic NSCLC
-First-line treatment of metastatic or unresectable, recurrent HNSCC
-Metastatic urothelial carcinoma
-Previously treated recurrent locally advanced or metastatic Esophageal Cancer
-Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy

For the MSI-H/dMMR indications, select patients for treatment with KEYTRUDA as a single agent based on MSI-H/dMMR status in tumor specimens. For the TMB-H indication, select patients for treatment with KEYTRUDA as a single agent based on TMB-H status in tumor specimens.

Because the effect of prior chemotherapy on test results for tumor mutation burden (TMB-H), MSI-H, or dMMR in patients with high-grade gliomas is unclear, it is recommended to test for these markers in the primary tumor specimens obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas.

Patient Selection for Combination Therapy

For use of KEYTRUDA in combination with chemotherapy, select patients based on the presence of positive PD L1 expression (CPS ≥1) in locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
For use of KEYTRUDA in combination with chemotherapy, with or without bevacizumab, select patients based on the presence of positive PD L1 expression in persistent, recurrent, or metastatic cervical cancer.
For use of KEYTRUDA in combination with chemotherapy, select patients based on the presence of positive PD-L1 expression in locally recurrent unresectable or metastatic TNBC

Recommended Dosage for Melanoma:

The recommended dose of KEYTRUDA in patients with unresectable or metastatic melanoma is 200 mg or 2 mg/kg, according to treating physician's discretion, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
The recommended dose of KEYTRUDA for the treatment of pediatric patients (12 years and older) with unresectable or metastatic melanoma is 2 mg/kg (up to a maximum of 200 mg) administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence or unacceptable toxicity.
The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months.
The recommended dose of KEYTRUDA for the adjuvant treatment of pediatric patients (12 years and older) with melanoma is 2 mg/kg (up to a maximum of 200 mg) administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or up to 12 months.

Recommended Dosage for NSCLC:

For first-line treatment:
The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.
For second-line or greater treatment:
The recommended dose of KEYTRUDA is 200 mg or 2 mg/kg, according to treating physician's discretion, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
For adjuvant treatment:
The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with NSCLC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months.
For neoadjuvant/adjuvant treatment:
The recommended dose of KEYTRUDA for the neoadjuvant treatment of adult patients with resectable NSCLC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with chemotherapy for 12 weeks (4 doses of 200 mg every 3 weeks) or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent after surgery for 39 weeks (13 doses of 200 mg every 3 weeks) or until disease recurrence or unacceptable toxicity.

Recommended Dosage for MPM:

The recommended dose of KEYTRUDA in patients with MPM is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity or up to 24 months.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for HNSCC:

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for cHL

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for PMBCL

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for Urothelial Cancer

The recommended dose of KEYTRUDA in patients with locally advanced or metastatic urothelial cancer is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with enfortumab vedotin, administer KEYTRUDA after enfortumab vedotin when given on the same day. Refer to the Prescribing Information for enfortumab vedotin administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
The recommended dose of KEYTRUDA in patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until persistent or recurrent high-risk NMIBC, disease progression or unacceptable toxicity, or up to 24 months.

Recommended Dosage for MSI-H/dMMR Cancer

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in children is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for MSI-H/dMMR Colorectal Cancer (CRC)

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.

Recommended Dosage for Gastric Cancer

The recommended dose of KEYTRUDA in adult is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with trastuzumab and chemotherapy, administer KEYTRUDA prior to trastuzumab and chemotherapy when given on the same day. Refer to the prescribing information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for Esophageal Cancer

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months. When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day.
Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.

Recommended Dosage for Cervical Cancer

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or for KEYTRUDA up to 24 months.
The recommended dose of KEYTRUDA in adults in combination with chemoradiotherapy is 200 mg every 3 weeks for 5 or 6 cycles followed by 400 mg every 6 weeks, administered as an intravenous infusion over 30 minutes until disease progression, unacceptable toxicity, or for KEYTRUDA up to 24 months.
For combination therapy, administer KEYTRUDA prior to chemoradiotherapy or prior to chemotherapy with or without bevacizumab when given on the same day. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for Biliary Tract Cancer

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for MCC

The recommended dose of KEYTRUDA in adults is 200 mg or 2 mg/kg, according to treating physician's discretion, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Recommended Dosage for RCC

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg axitinib orally twice daily or in combination with lenvatinib 20 mg orally once daily until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months.
When axitinib is used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with RCC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months.

Recommended Dosage for Endometrial Carcinoma

The recommended dose of KEYTRUDA in adults in combination with chemotherapy is 200 mg every 3 weeks administered as an intravenous infusion over 30 minutes until disease progression, unacceptable toxicity, or for up to 6 cycles.
When KEYTRUDA is administrated alone for maintenance therapy, the recommended dose is 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes until disease progression, unacceptable toxicity, or for up to 24 months.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.
The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with lenvatinib 20 mg orally once daily until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months. Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Recommended Dosage for TMB-H Cancer

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
The recommended dose of KEYTRUDA in pediatric is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months.

Recommended Dosage for cSCC

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
The recommended dose of KEYTRUDA in patients with locally recurrent unresectable or metastatic TNBC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.

Recommended Dosage for TNBC

The recommended dose of KEYTRUDA in adult patients with high-risk early-stage TNBC for neoadjuvant treatment is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with chemotherapy for 24 weeks (8 doses of 200mg every 3 weeks) or until disease progression or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent for up to 27 weeks (9 doses of 200 mg every 3 weeks) or until disease recurrence or unacceptable toxicity.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate. Patients who experience disease progression or unacceptable toxicity related to KEYTRUDA with neoadjuvant treatment in combination with chemotherapy should not receive adjuvant single agent KEYTRUDA.

The recommended dose of KEYTRUDA in patients with locally recurrent unresectable or metastatic TNBC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, for recommended dosing information, as appropriate.

Dose Modifications

No dose reduction for KEYTRUDA is recommended. In general, withhold KEYTRUDA for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue KEYTRUDA for Life-threatening (Grade 4) immune- mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids.
Dosage modifications for KEYTRUDA for adverse reactions that require management different from these general guidelines are summarized in Table 1 & Table 2 of Dosage Modifications section in the full Prescribing Information (PI).
Recommended Dose Modifications for Adverse Reactions for KEYTRUDA in Combination with Lenvatinib
When administering KEYTRUDA in combination with Lenvatinib, modify the dosage of one or both drugs. Withhold or discontinue KEYTRUDA as shown in Table 1 of Dosage Modifications (section 2.20) in the full PI. Refer to Lenvatinib prescribing information for additional dose modification information.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients listed in section 11 of the Prescribing Information.
DRUG INTERACTION: No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA.

WARNINGS AND PRECAUTIONS:

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 PD-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. Important immune-mediated adverse reactions listed under WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. 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. 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 immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence of pneumonitis 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%) adverse reactions. Systemic corticosteroids were required in 67% (63/94) of patients with pneumonitis.
Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) of patients and withholding of KEYTRUDA in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence of pneumonitis. Pneumonitis resolved in 59% of the 94 patients.
In clinical studies enrolling 389 adult patients with cHL who received KEYTRUDA as a single agent, pneumonitis occurred in 31 (8%) patients, including Grades 3-4 pneumonitis 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 21 (5.4%) patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.
In a clinical study enrolling 580 adult patients with resected NSCLC (KEYNOTE-091) who received KEYTRUDA as a single agent for adjuvant treatment, pneumonitis occurred in 41 (7%) patients, 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 (CMV) 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%) adverse reactions. Systemic corticosteroids were required in 69% (33/48) of patients with colitis. Additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) of patients and withholding of KEYTRUDA in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence of colitis. Colitis resolved in 85% of the 48 patients.

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%) adverse reactions. Systemic corticosteroids were required in 68% (13/19) of patients with hepatitis. Eleven percent of these patients required additional immunosuppressant therapy. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) of patients and withholding of KEYTRUDA in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence of hepatitis. Hepatitis resolved in 79% of the 19 patients.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, 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%) adverse reactions. Systemic corticosteroids were required in 77% (17/22) of patients with adrenal insufficiency; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) of patients and withholding of KEYTRUDA 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%) adverse reactions. Systemic corticosteroids were required in 94% (16/17) of patients with hypophysitis; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) of patients and withholding of KEYTRUDA in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.