Keytruda (pembrolizumab) dosing, indications, interactions, adverse effects, and more (original) (raw)
Dosage Forms & Strengths
injectable solution
- 100mg/4mL (25mg/mL)
Melanoma
Unresectable or metastatic melanoma
- Indicated for treatment of unresectable or metastatic melanoma
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression or unacceptable toxicity
Adjuvant treatment
- Indicated for adjuvant treatment of adults with Stage IIB, IIC, or III melanoma following complete resection
- 200 mg IV q3Weeks OR 400 mg q6Weeks
- Continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence
Non-Small Cell Lung Cancer
Single-agent for localized disease
- Indicated as adjuvant treatment following resection and platinum-based chemotherapy for Stage IB (T2a ≥4 cm), II, or IIIA NSCLC
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression or unacceptable toxicity, or up to 12 months without disease progression
Single-agent for unresectable or advanced disease
- First-line treatment of patients with stage III non-small cell lung cancer (NSCLC), who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 [Tumor Proportion Score (TPS) ≥1%)], with no EGFR or ALK genomic tumor aberrations
- Metastatic NSCLC whose tumors with PD-L1 expression (TPS ≥1%) and disease progression on or after platinum-containing chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression or unacceptable toxicity, or up to 24 months without disease progression
Combination therapy for resectable NSCLC
- Indicated for resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery
- 200 mg IV q3Weeks OR 400 mg q6Weeks
- Administer before chemotherapy if given on the same day
- Neoadjuvant treatment in combination with chemotherapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by pembrolizumab as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity
Combination therapy for metastatic NSCLC
- Metastatic nonsquamous NSCLC: First-line treatment in combination with pemetrexed and platinum chemotherapy with no EGFR or ALK genomic tumor aberrations
- Metastatic squamous NSCLC: First-line treatment in combination with carboplatin and either paclitaxel or paclitaxel protein bound
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
- See prescribing information for chemotherapy agents doses administered in combination with pembrolizumab
Head & Neck Squamous Cell Carcinoma
Single-agent therapy
- Indicated for first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1]
- Indicated for treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression
Combination therapy
- Indicated in combination with platinum and fluorouracil (FU) for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression
Classical Hodgkin Lymphoma
Indicated for relapsed or refractory classical Hodgkin lymphoma (cHL)
200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Primary Mediastinal Large B-Cell Lymphoma
Indicated for refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after ≥2 prior lines of therapy
200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Urothelial Carcinoma
Combination with enfortumab
- Indicated for locally advanced or metastatic urothelial carcinoma
- 200 mg IV q3Weeks OR 400 mg q6Weeks
- Administer pembrolizumab ~30 minutes after enfortumab vedotin when given on the same day
- Continue until disease progression, unacceptable toxicity, or up to 24 months
Single-agent therapy
Locally advanced or metastatic urothelial carcinoma
- Indicated for locally advanced or metastatic urothelial carcinoma in patients who are ineligible for any platinum-containing chemotherapy or have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Bacillus Calmette-Guerin (BCG)-unresponsive bladder cancer
- Indicated for treatment of BCG-unresponsive, high-risk, nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors in patients who are ineligible for, or have elected not to undergo cystectomy
- 200 mg IV q3Weeks OR 400 mg q6Weeks until persistent or recurrent high-risk NMIBC, disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression
Microsatellite Instability-High Cancer
Indicated for unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have solid tumors that have progressed following prior treatment and in patients who have no satisfactory alternative treatment options
200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
Indicated for unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC)
200 mg IV q3Weeks or 400 mg IV q6Weeks
Continue until disease progression, unacceptable toxicity, or up to 24 months
Gastric Cancer
Indicated in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
Also, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma
200 mg IV q3Weeks OR 400 mg q6Weeks PLUS trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy
Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Esophageal Cancer
Indicated for recurrent locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1-5 cm above GEJ) carcinoma in patients who are not candidates for surgical resection or definitive chemoradiation
Specifically used either
- In combination with platinum- and fluoropyrimidine-based chemotherapy, or
- As a single agent after ≥1 prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10)
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression
Cervical Cancer
Single-agent therapy
- Indicated for recurrent or metastatic cervical cancer in adults with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1)
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Combination chemotherapy
- Indicated in combination with chemotherapy, with or without bevacizumab, for persistent, recurrent, or metastatic cervical cancer in adults whose tumors express PD-L1 (CPS ≥1)
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
- Refer to prescribing information for agents used in combination
Combination chemoradiotherapy
- Indicated in combination with chemoradiotherapy for patients with FIGO 2014 Stage III-IVA cervical cancer
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Hepatocellular Carcinoma
Indicated for treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD1/PD-L1-containing regimen
200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Merkel Cell Carcinoma
Indicated for treatment of recurrent, locally advanced, or metastatic Merkel cell carcinoma (MCC)
200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Renal Cell Carcinoma
Combination therapy with axitinib
- Indicated in combination with axitinib, for first-line treatment of patients with advanced renal cell carcinoma (RCC)
- Pembrolizumab 200 mg IV q3Weeks OR 400 mg q6Weeks, PLUS
- Axitinib 5 mg PO BID (initial dose)
- Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression
- When axitinib is used in combination with pembrolizumab, consider dose escalation of axitinib above the initial 5 mg dose at ≥6 weeks intervals
- Refer also prescribing information for axitinib dosing information
Combination therapy with lenvatinib
- Indicated in combination with lenvatinib, for first-line treatment of patients with advanced RCC
- Pembrolizumab 200 mg IV q3Weeks OR 400 mg q6Weeks, PLUS
- Lenvatinib 20 mg PO qDay
- Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression
Adjuvant treatment
- Indicated for adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease recurrence, unacceptable toxicity, or for up to 12 months
Endometrial Cancer
Combination therapy with lenvatinib
- Indicated in combination with lenvatinib for patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation
- 200 mg IV q3Weeks OR 400 mg q6Weeks, PLUS
- Lenvatinib 20 mg PO qDay
- Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months
- Refer to the lenvatinib prescribing information for recommended dosing information
Combination with carboplatin and paclitaxel chemotherapy
- Indicated for primary advanced or recurrent endometrial carcinoma in combination with carboplatin and paclitaxel followed by single-agent pembrolizumab
- 200 mg IV q3Weeks OR 400 mg q6Week
- Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months
- Administer before chemotherapy if given on the same day
Single-agent therapy
- Indicated for advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, in patients who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation
- 200 mg IV q3Weeks OR 400 mg q6Week
- Continue until disease progression, unacceptable toxicity, or up to 24 months
Tumor Mutational Burden-High Cancer
Indicated for unresectable or metastatic tumor mutational burden-high (TMB-H) (≥10 mutations/megabase [mut/Mb]) solid tumors in adult and pediatric patients that have progressed following prior treatment and who have no satisfactory alternative treatment options
200 mg IV q3Weeks OR 400 mg q6Weeks
Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Cutaneous Squamous Cell Carcinoma
Indicated for treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not incurable by surgery or radiation
200 mg IV q3Weeks OR 400 mg q6Weeks
Continue until disease progression or unacceptable toxicity, or up to 24 months without disease progression
Breast Cancer
High-risk early-stage triple-negative breast cancer (TNBC)
- Indicated for the treatment of patients with high-risk, early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery
Neoadjuvant treatment
- In combination with chemotherapy: 200 mg IV q3Weeks for 8 doses or 400 mg IV q6Weeks for 4 doses or until disease progression or unacceptable toxicity
- Followed by single agent adjuvant therapy
Adjuvant treatment
- Single-agent therapy: 200 mg IV q3Weeks for 9 doses or 400 mg IV q6Weeks for 5 doses or until disease progression or unacceptable toxicity
Locally recurrent unresectable or metastatic TNBC
- Indicated, in combination with chemotherapy, for locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) who tumors express PD-L1 (CPS ≥10)
- 200 mg IV q3Weeks or 400 mg IV q6Weeks
- Continue until disease progression, unacceptable toxicity, or up to 24 months
- Administer prior to chemotherapy when given on the same day
Biliary Tract Cancer
Indicated for locally advanced, unresectable, or metastatic biliary tract cancer (BTC) in combination with gemcitabine and cisplatin
200 mg IV q3Weeks or 400 mg IV q6Weeks
Administer before chemotherapy when given on same day
Continue until disease progression, unacceptable toxicity, or up to 24 months
Malignant Pleural Mesothelioma
Indicated in combination with pemetrexed and platinum chemotherapy for first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma (MPM)
200 mg IV q3Weeks or 400 mg IV q6Weeks
Administer before chemotherapy when given on same day
Continue until disease progression, unacceptable toxicity, or up to 24 months
Refer to prescribing information for agents used in combination
Dosage Modifications
Renal impairment (eGFR ≥15 mL/min/1.73 m²): No dosage adjustment required
Hepatic impairment
- Mild: No dosage adjustment required
- Moderate or severe: Pharmacokinetics of pembrolizumab is unknown
Interrupt or slow infusion rate
- Grades 1 or 2 infusion-related reactions
Withhold dose (resume when recover to Grade <1)
- Grade 3 or 4 endocrinopathies (eg, hypophysitis, hypo- or hyperthyroidism)
- Grade 4 hematological toxicity in cHL or PMBCL
- Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
- Immune-mediated hepatitis in patients without HCC: AST/ALT>3 and up to 5x upper limit of normal (ULN) or total bilirubin >1.5 and up to 3x ULN
Withhold (resume when recover to Grade <1 after corticosteroid taper)
- Grade 2 immune-mediated pneumonitis
- Grades 2 or 3 immune-mediated colitis
- Grade 2 immune-mediated nephritis
- Any other Grade 2 or 3 immune-mediated adverse reaction, based on the severity and type of reaction
Withhold dose (resume when AST/ALT and total bilirubin recover to Grades <1 or to baseline)
Immune-mediated hepatitis in patients with HCC
- AST/ALT ≥5x ULN if baseline <2x ULN
- AST/ALT >3x baseline if baseline ≥2x ULN
- Total bilirubin >2 mg/dL if baseline <1.5 mg/dL
- Total bilirubin >3 mg/dL, regardless of baseline levels
RCC treated with pembrolizumab with axitinib
- ALT or AST ≥3x ULN but <10x ULN with concurrent total bilirubin ≥2x ULN: Withhold both drugs and consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery; if rechallenging with axitinib, consider dose reduction as per axitinib prescribing information
- ALT or AST ≥10x ULN or ≥3x ULN with concurrent total bilirubin ≥2x ULN: Permanently discontinue both drugs and consider corticosteroid therapy
Permanently discontinue for any of the following
- Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
- Grades 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
- Grades 3 or 4 nephritis
- Grades 4 severe skin reactions or confirmed SJS or TEN
- Grades 3 or 4 infusion-related reactions
- Grades 2 or 3 adverse reaction (excluding endocrinopathy) lasting ≥12 week after last dose
- Grade 3 (based on severity) or Grade 4 other immune-mediated adverse reactions
- Grade 4 immune-mediated colitis
Immune-mediated hepatitis in patients with HCC
- ALT/AST >10x ULN; or Child-Pugh score ≥9 points
- Gastrointestinal bleeding suggestive of portal hypertension
- New onset of ascites or encephalopathy
Immune-mediated hepatitis in patients without HCC
- Patients without liver metastases: AST/ALT >5x ULN or total bilirubin >3x ULN
- Patients with liver metastasis and Grade 2 AST/ALT at baseline: With an increase in AST/ALT ≥50% relative to baseline that persists for ≥1 week
Dosing Considerations
Limitation of use
- Not recommended for PMBCL in patients who require urgent cytoreductive therapy
Patient selection
Information on FDA-approved tests is available at: https://www.fda.gov/CompanionDiagnostics
PD-L1 expression
NSCLC (single-agent, non-adjuvant therapy)
- Verify PD-L1 Tumor Proportion Score ≥1%
HNSCC (single-agent, first-line therapy for advanced disease)
- Verify PD-L1 Combined Positive Score (CPS) ≥1%
Gastric cancer (HER2+, combination therapy)
- Verify PD-L1 CPS ≥1%
Esophageal cancer (squamous cell histology, single-agent therapy)
- Verify PD-L1 CPS ≥10%
Cervical cancer (single-agent or combination therapy)
- Verify PD-L1 CPS ≥1%
TNBC (single-agent therapy)
- Verify PD-L1 CPS ≥10%
MSI-H/dMMR solid tumors
Confirm MSI-H/dMMR status in tumor specimens
Endometrial carcinoma (combination therapy with lenvatinib)
- Use an FDA-approved test to select patients do not have MSI-H mutations
Non-colorectal cancer solid tumors
- If unable to perform confirmatory MSI-H/dMMR testing, may use presence of TMB ≥10 mutations/megabase to select patients
High-grade gliomas (off-label use)
- Test for MSI-H and dMMR status in the primary tumor specimens obtained before initiation of temozolomide chemotherapy
TMB-H solid tumors
Verify TMB-H status (≥10 mutations/megabase) in tumor specimens
High-grade gliomas (off-label use)
- Test for TMB-H status in the primary tumor specimens obtained before initiation of temozolomide chemotherapy
Orphan Designations
Multiple myeloma
Nasopharyngeal carcinoma
Follicular lymphoma
Sponsor
- Merck, Sharp & Dohme a subsidiary of Merck & Co, Inc; One Merck Drive, Whitehouse Station, NJ 08889
Dosage Forms & Strengths
injectable solution
- 100mg/4mL (25mg/mL)
Classical Hodgkin Lymphoma
Indicated for refractory classical Hodgkin lymphoma (cHL) or relapse after ≥2 prior lines of therapy
2 mg/kg IV q3Weeks; not to exceed 200 mg/dose
Continue until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression
Microsatellite Instability-High Cancer
Indicated for unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have:
- Solid tumors that have progressed following prior treatment and in patients who have no satisfactory alternative treatment options, OR
- Colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
2 mg/kg IV q3Weeks; not to exceed 200 mg/dose
Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Primary Mediastinal Large B-Cell Lymphoma
Indicated for refractory primary mediastinal large B-cell lymphoma (PMBCL), or relapse after ≥2 prior lines of therapy
2 mg/kg IV q3Weeks; not to exceed 200 mg/day
Merkel Cell Carcinoma
Indicated for treatment of recurrent, locally advanced, or metastatic Merkel cell carcinoma (MCC)
2 mg/kg IV q3Weeks; not to exceed 200 mg/dose
Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Tumor Mutational Burden-High Cancer
Indicated for unresectable or metastatic tumor mutational burden-high (TMB-H) (≥10 mutations/megabase [mut/Mb]) solid tumors in adult and pediatric patients that have progressed following prior treatment and who have no satisfactory alternative treatment options
2 mg/kg IV q3Weeks; not to exceed 200 mg/dose
Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Melanoma
Indicated for adjuvant treatment of adult and pediatric patients aged ≥12 years with Stage IIB, IIC, or III melanoma following complete resection
2 mg/kg IV q3Weeks; not to exceed 200 mg/dose
Continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence
Dosage Modifications
Renal impairment: No dosage adjustment required
Hepatic impairment
- Mild: No dosage adjustment required
- Moderate or severe: Not studied
Interrupt or slow infusion rate
- Grades 1 or 2 infusion-related reactions
Withhold dose (resume when recover to Grade <1)
- Grade 3 or 4 endocrinopathies (eg, hypophysitis, hypo- or hyperthyroidism)
- Grade 4 hematological toxicity in cHL or PMBCL
- Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
- Immune-mediated hepatitis in patients without HCC: AST/ALT>3 and up to 5x upper limit of normal (ULN) or total bilirubin >1.5 and up to 3x ULN
Withhold (resume when recover to Grade <1 after corticosteroid taper)
- Grade 2 immune-mediated pneumonitis
- Grades 2 or 3 immune-mediated colitis
- Grade 2 immune-mediated nephritis
- Any other Grade 2 or 3 immune-mediated adverse reaction, based on the severity and type of reaction
Permanently discontinue for any of the following
- Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
- Grades 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
- Grades 3 or 4 nephritis
- Grades 4 severe skin reactions or confirmed SJS or TEN
- Grades 3 or 4 infusion-related reactions
- Grades 2 or 3 adverse reaction (excluding endocrinopathy) lasting ≥12 week after last dose
- Grade 3 (based on severity) or Grade 4 other immune-mediated adverse reactions
- Grade 4 immune-mediated colitis
Immune-mediated hepatitis in patients without HCC
- Patients without liver metastases: AST/ALT >5x ULN or total bilirubin >3x ULN
- Patients with liver metastasis and Grade 2 AST/ALT at baseline: With an increase in AST/ALT ≥50% relative to baseline that persists for ≥1 week
Dosing Considerations
Limitations of use
- Safety and effectiveness in pediatric patients with MSI-H or TMB-H central nervous system cancers have not been established
- Not recommended for treatment of PMBCL who require urgent cytoreductive therapy
Patient selection
Information on FDA-approved tests is available at: https://www.fda.gov/CompanionDiagnostics
MSI-H/dMMR solid tumors
- Confirm MSI-H/dMMR status in tumor specimens
Endometrial carcinoma (combination therapy with lenvatinib)
- Use an FDA-approved test to select patients do not have MSI-H mutations
Non-colorectal cancer solid tumors
- If unable to perform confirmatory MSI-H/dMMR testing, may use the presence of TMB ≥10 mutations/megabase to select patients
High-grade gliomas (off-label use)
- Test for MSI-H and dMMR status in the primary tumor specimens obtained before initiation of temozolomide chemotherapy
TMB-H solid tumors
Verify TMB-H status (≥10 mutations/megabase) in tumor specimens
High-grade gliomas (off-label use)
- Test for TMB-H status in the primary tumor specimens obtained before initiation of temozolomide chemotherapy