What is Keytruda (pembrolizumab) usually used for?

What is Keytruda (Pembrolizumab) Used For?

Keytruda (pembrolizumab) is a PD-1 immune checkpoint inhibitor primarily used to treat multiple types of advanced cancers, including melanoma, non-small cell lung cancer, head and neck cancer, bladder cancer, kidney cancer, and various other solid tumors, particularly those with high PD-L1 expression or specific biomarkers like microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). 1, 2

Primary Cancer Indications

Melanoma

• First-line treatment for unresectable or metastatic melanoma 2, 3
• Adjuvant therapy after surgical resection for Stage IIB, IIC, or Stage III melanoma in adults and children ≥12 years to prevent recurrence 2
• Demonstrated superior progression-free survival, overall survival, and response rates compared to ipilimumab in treatment-naïve patients 3, 4

Non-Small Cell Lung Cancer (NSCLC)

• First-line monotherapy when PD-L1 expression ≥50% (Tumor Proportion Score) without EGFR or ALK mutations, with median overall survival of 30 months versus 14 months with chemotherapy 1, 5
• Combined with platinum-based chemotherapy (pemetrexed for nonsquamous, carboplatin/paclitaxel for squamous) regardless of PD-L1 status 1, 2
• Neoadjuvant/adjuvant therapy for early-stage resectable NSCLC combined with chemotherapy, then continued alone after surgery 2
• Adjuvant monotherapy for Stage IB (≥4 cm), II, or IIIA NSCLC after complete resection and platinum-based chemotherapy 2
• Second-line therapy after platinum-based chemotherapy failure in PD-L1-positive tumors 1, 5

Head and Neck Squamous Cell Carcinoma (HNSCC)

• First-line treatment combined with fluorouracil and platinum for recurrent or metastatic disease 6, 2
• First-line monotherapy when PD-L1 positive for unresectable recurrent/metastatic disease 6, 2
• Second-line therapy after platinum-based chemotherapy failure 6, 2

Urothelial (Bladder) Cancer

• First-line therapy for cisplatin-ineligible patients with PD-L1 expression (combined positive score ≥10) 1, 6
• Second-line therapy (category 1 recommendation) after platinum-based chemotherapy progression, showing median overall survival of 10.3 months versus 7.4 months with chemotherapy 1, 6

Renal Cell Carcinoma (RCC)

• First-line combination with axitinib or lenvatinib for advanced/metastatic disease 2
• Adjuvant monotherapy for intermediate-high or high-risk RCC after nephrectomy to prevent recurrence 2

Gastrointestinal Cancers

• Gastric/gastroesophageal junction cancer: First-line with fluoropyrimidine and oxaliplatin-based chemotherapy for HER2-negative tumors with PD-L1 CPS ≥5 (category 1) 1
• Colorectal cancer: First-line for MSI-H/dMMR metastatic disease 5, 6
• Biliary tract cancer: Combined with gemcitabine and cisplatin for unresectable/metastatic disease 2
• Hepatocellular carcinoma: After prior systemic therapy in hepatitis B-associated HCC 2

Gynecologic Cancers

• Cervical cancer: Combined with chemotherapy ± bevacizumab for persistent/recurrent/metastatic PD-L1-positive disease, or with chemoradiation for Stage III-IVA disease 2
• Endometrial carcinoma: Combined with carboplatin/paclitaxel for advanced disease, or with lenvatinib for pMMR/non-MSI-H tumors after prior therapy 2

Breast Cancer

• Triple-negative breast cancer (TNBC): Combined with chemotherapy as neoadjuvant/adjuvant treatment for early-stage high-risk disease, or with chemotherapy for PD-L1-positive metastatic disease 1, 2

Other Solid Tumors

• Classical Hodgkin lymphoma: After failed prior therapies in adults, or after ≥2 prior treatments in children 2
• Merkel cell carcinoma: For metastatic or recurrent disease in adults and children 2
• Cutaneous squamous cell carcinoma: For recurrent/metastatic disease not curable by surgery/radiation 2
• Malignant pleural mesothelioma: Combined with pemetrexed and platinum as first-line for unresectable disease 2

Biomarker-Driven Indications

Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR)

• Tissue-agnostic approval for any unresectable/metastatic solid tumor after prior treatment failure with no satisfactory alternatives 1, 6
• Objective response rate of 39.6% across multiple tumor types, with 78% of responses lasting ≥6 months 1

Tumor Mutational Burden-High (TMB-H)

• Tissue-agnostic approval for solid tumors with ≥10 mutations/megabase after prior treatment failure 1, 6, 2
• Response rate of 29% with 50% of responses lasting ≥24 months 1
• Not effective in TMB-H central nervous system cancers 2

NTRK Gene Fusions

• While pembrolizumab is not specifically indicated for NTRK fusion-positive tumors, these patients should receive NTRK inhibitors (larotrectinib or entrectinib) as preferred therapy 1

Key Biomarker Testing Requirements

• PD-L1 testing is mandatory for certain indications (NSCLC monotherapy, HNSCC first-line, cervical cancer, urothelial cancer) 5, 6
• MSI/MMR status should be determined before initiating therapy in colorectal, gastric, and endometrial cancers 5, 6
• TMB testing may identify additional responders across tumor types 6

Important Clinical Considerations

Response Patterns

• Median time to response is approximately 3 months (first assessment at 12 weeks) 5
• Pseudoprogression can occur—initial disease progression may precede response, requiring careful clinical assessment before discontinuing therapy 5
• Late responses beyond 1 year are possible 5
• Complete responses are highly durable (88% persisting at 30 months median follow-up) 5

Safety Profile

• Grade 3-5 treatment-related adverse events occur in 13-16% of patients, significantly lower than chemotherapy (35%) 5, 7
• Immune-related adverse events include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions 1, 8, 2
• Treatment-related deaths are rare but can occur, particularly with combination regimens 1

Contraindications and Precautions

• Avoid in severe autoimmune disease or solid organ transplant recipients due to risk of rejection 1, 2
• Monitor for infusion reactions (chills, rash, flushing, shortness of breath, dizziness) 2
• Pregnancy category: Can harm unborn baby; effective contraception required during treatment and for 4 months after last dose 2

Special Populations

• Elderly patients (>65 years) show equivalent efficacy and no increased toxicity compared to younger patients 5
• Pediatric approval exists for melanoma (≥12 years), Hodgkin lymphoma, Merkel cell carcinoma, and MSI-H/TMB-H solid tumors (excluding CNS tumors) 2

Common Pitfalls to Avoid

• Do not use pembrolizumab in proficient mismatch repair colorectal cancer even if TMB-high, as it is ineffective 5
• Do not discontinue prematurely for initial progression—29% of MSI-H colorectal cancer patients show initial progression despite overall survival benefit 5
• Higher PD-L1 expression correlates with better response, but unselected patients may still benefit compared to chemotherapy in certain settings 5
• Smoking reduces erlotinib bioavailability and may affect outcomes; smoking cessation should be strongly encouraged 1