Checkpoint Inhibitor Evidence: EMPOWER and C-POST Trials

Dr. Park reviews the three FDA-approved checkpoint inhibitors in cSCC: cemiplimab (approved 2018), pembrolizumab (KEYNOTE-629), and cosibelimab, a PD-L1 inhibitor approved in 2024 with an updated 2025 label based on the 301-101 study. Overall response rates range from approximately 35% to 50% across trials, with the depth and durability of responses being particularly practice-changing. The EMPOWER-CSCC-1 trial, featuring the largest and most mature dataset for PD-1 inhibition in cSCC, demonstrated a ~47% ORR with durable, ongoing responses, a major advance over prior chemotherapy and EGFR-targeted options.

Dr. Schoenfeld then addresses the C-POST trial, which evaluated adjuvant cemiplimab in high-risk patients following curative surgery and radiation. Eligible patients had features predictive of recurrence: nodes >2 cm, extranodal extension, more than 3 involved lymph nodes, T4 lesions, in-transit metastases, or recurrent disease. Approximately 48 weeks of cemiplimab significantly improved disease-free survival with a hazard ratio of ~0.68. Dr. Singh notes that KEYNOTE-630, which assessed adjuvant pembrolizumab, failed to meet its primary endpoint and was discontinued, underscoring the importance of being guided by available data. The panel agrees that multidisciplinary communication is essential to ensure high-risk patients are not lost between providers and understand the full treatment regimen.