Is Pemgarda (pembrolizumab) still indicated for cancer treatment?

Pembrolizumab (Keytruda) Remains Indicated for Multiple Cancer Types

Yes, pembrolizumab (Keytruda) is still indicated for cancer treatment across multiple cancer types, with FDA approvals for head and neck cancers, lung cancer, bladder cancer, colorectal cancer, and other malignancies based on specific biomarkers. 1, 2

Current Indications for Pembrolizumab

Head and Neck Squamous Cell Carcinoma (HNSCC)

• FDA approved in 2016 for recurrent or metastatic HNSCC that has progressed on or after platinum-based chemotherapy 1, 3
• NCCN recommends pembrolizumab as a category 2A treatment option for this indication 1
• Response rates appear durable, with 6-month overall survival rate of 59% and progression-free survival rate of 23% in clinical trials 1
• Higher response rates observed in PD-L1 positive tumors (≥1% expression) compared to PD-L1 negative tumors (22% vs 4%, p=0.021) 1

Non-Small Cell Lung Cancer (NSCLC)

• Approved for first-line treatment of metastatic NSCLC with high PD-L1 expression (Tumor Proportion Score ≥50%) with no EGFR or ALK genomic aberrations 1, 4
• Also indicated for second-line treatment of metastatic NSCLC with PD-L1 expression (TPS ≥1%) with disease progression on or after platinum-containing chemotherapy 1, 4
• In the KEYNOTE-024 study, pembrolizumab showed significant improvement in overall survival (HR 0.60) and progression-free survival (HR 0.50) compared to chemotherapy in previously untreated NSCLC 1, 4
• Particularly pronounced benefit in squamous cell lung cancer subgroup (HR 0.35) 1

Bladder Cancer (Urothelial Carcinoma)

• Approved for locally advanced or metastatic urothelial carcinoma that has progressed during or after platinum-based chemotherapy 1
• Also approved as first-line treatment for patients who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (combined positive score ≥10) 1
• Received category 1 recommendation as second-line therapy based on phase III trial showing longer median overall survival compared to chemotherapy (10.3 vs 7.4 months, p=0.002) 1
• Associated with fewer grade 3-5 treatment-related adverse events compared to chemotherapy (15.0% vs 49.4%) 1

Colorectal Cancer

• Recommended for mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer 1
• Can be used in first-line or non-first-line settings for dMMR/MSI-H or POLE/POLD1 mutation-positive metastatic colorectal cancer 1
• In clinical trials, immune-related objective response rates were 40% in dMMR colorectal cancer compared to 0% in MMR-proficient colorectal cancer 1

Rare Head and Neck Cancers

• May be offered to patients with tumor mutational burden (TMB)-high recurrent or metastatic rare head and neck cancers 1
• Also recommended for recurrent or metastatic salivary gland cancers with PD-L1 expression ≥1% 1
• Based on KEYNOTE-158 study showing higher response rates in TMB-high tumors compared to non-TMB high tumors (29% vs 6%) 1

Biomarkers for Pembrolizumab Response

• PD-L1 expression: Important biomarker for response in multiple tumor types 1
• Microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR): Predictive of response across tumor types 1
• Tumor mutational burden (TMB): High TMB associated with better response to pembrolizumab 1

Safety Profile

• Generally well-tolerated with grade 3/4 toxicities reported in 9-16% of patients across studies 1
• Common immune-related adverse events include pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions 2, 3, 5
• Immune-related cutaneous adverse events such as lichenoid dermatitis have been reported 5

Clinical Considerations

• Pembrolizumab is administered as an intravenous infusion at a dose of 200 mg every 3 weeks 2
• Half-life is approximately 22 days 2
• No clinically important effect on clearance based on age, sex, race, renal impairment, or mild to moderate hepatic impairment 2
• Treatment should be continued until disease progression or unacceptable toxicity 2

Pitfalls and Caveats

• Response to pembrolizumab may vary based on biomarker status - proper testing for PD-L1, MSI/MMR status, or TMB is essential before initiating therapy 1
• Patients with autoimmune diseases, conditions requiring immunosuppression, or active infections may not be suitable candidates for pembrolizumab therapy 2
• Immune-related adverse events can occur during treatment and require prompt recognition and management 2, 5
• Different tumor types may require different PD-L1 expression thresholds for optimal patient selection 1