Headline: Adjuvant cemiplimab improves disease free survival following adjuvant radiation in patients with resected, high risk, cutaneous squamous cell carcinoma (cSCC).
The Study: Immunotherapy is currently indicated for patients with advanced cSCC that is not eligible for curative surgery or radiation. But we’ve all seen cases of advanced cSCC where it seems adjuvant immunotherapy would be beneficial. The phase 3 C-post trial randomized 415 patients with high-risk cSCC following resection and adjuvant radiation to +/- cemiplimab versus placebo for up to 48 weeks. “High-risk” here was pretty high risk: in-transit mets, perineural invasion of named nerves, T4 primary tumor (with bone invasion), a local recurrence ≥4 cm or ≥2 cm + poorly-differentiated, or high nodal burden including a nodal deposit ≥2 cm with extracapsular extension or ≥3 involved nodes. Table 1 provides an excellent summary of high-risk features included. Surgery had to achieve a “macroscopic gross resection” so presumably R1 resections were allowed, and radiation comprised “a biologically equivalent dose of at least 50 Gy.” Cemiplimab was delivered at 350 mg q3 weeks x 4 with an amendment allowing transitioning to 700 mg q6 weeks x 6 for a total of 48 weeks. The primary endpoint of disease-free survival was significantly improved from 64% to 87% at 24 months. Locoregional recurrences were reduced to 40 → 9 (HR 0.20) and distant mets from 26 → 10 (HR 0.35). Survival analysis is not mature, but it should actually mean something here as 51/61 patients with recurrence (84%) crossed over to receive salvage cemiplimab upon progression.
TBL:Adjuvant cemiplimab following surgery and radiation for high risk cSCC significantly improves disease free survival. | Rischin, N Engl J Med 2025
The Study: Immunotherapy is currently indicated for patients with advanced cSCC that is not eligible for curative surgery or radiation. But we’ve all seen cases of advanced cSCC where it seems adjuvant immunotherapy would be beneficial. The phase 3 C-post trial randomized 415 patients with high-risk cSCC following resection and adjuvant radiation to +/- cemiplimab versus placebo for up to 48 weeks. “High-risk” here was pretty high risk: in-transit mets, perineural invasion of named nerves, T4 primary tumor (with bone invasion), a local recurrence ≥4 cm or ≥2 cm + poorly-differentiated, or high nodal burden including a nodal deposit ≥2 cm with extracapsular extension or ≥3 involved nodes. Table 1 provides an excellent summary of high-risk features included. Surgery had to achieve a “macroscopic gross resection” so presumably R1 resections were allowed, and radiation comprised “a biologically equivalent dose of at least 50 Gy.” Cemiplimab was delivered at 350 mg q3 weeks x 4 with an amendment allowing transitioning to 700 mg q6 weeks x 6 for a total of 48 weeks. The primary endpoint of disease-free survival was significantly improved from 64% to 87% at 24 months. Locoregional recurrences were reduced to 40 → 9 (HR 0.20) and distant mets from 26 → 10 (HR 0.35). Survival analysis is not mature, but it should actually mean something here as 51/61 patients with recurrence (84%) crossed over to receive salvage cemiplimab upon progression.
TBL:Adjuvant cemiplimab following surgery and radiation for high risk cSCC significantly improves disease free survival. | Rischin, N Engl J Med 2025