Dr Patel on the Potential for Adjuvant Immunotherapy in CSCC

“When we resect these squamous cell cancers of the skin, often there’s a question [of whether] we should follow the [same] paradigm we follow with melanoma of the skin. Should we be giving [patients] immunotherapy after surgery?”

Sapna Patel, MD, professor, Division of Medical Oncology; leader, Cutaneous Oncology Program; William Robinson Endowed Chair in Cancer Research, University of Colorado Cancer Center, discusses the potential for immunotherapy as adjuvant therapy in patients with high-risk cutaneous squamous cell carcinoma (CSCC).

A common question within the CSCC space is whether patients could be treated with adjuvant immunotherapy, Patel begins. It remains unclear whether the adjuvant treatment paradigm for patients with melanoma should be followed in the CSCC realm, especially for patients at high risk of recurrence who could potentially benefit from adjuvant immunotherapy, she says.

Studies exploring adjuvant immunotherapy strategies in CSCC included the phase 3 KEYNOTE-630 trial (NCT03833167) evaluating pembrolizumab (Keytruda) vs placebo as adjuvant treatment for patients with high-risk, locally advanced CSCC, Patel notes. However, in August 2024, the study’s data monitoring committee recommended the trial be discontinued for futility after the treatment of pembrolizumab vs placebo did not demonstrate a statistically significant improvement in recurrence-free survival, the trial’s primary end point. Therefore, adjuvant pembrolizumab may not be beneficial in this patient population, Patel emphasizes.

Furthermore, the phase 3 C-POST trial (NCT03969004) is evaluating adjuvant cemiplimab-rwlc (Libtayo) vs placebo in patients with high-risk CSCC. The study met its primary end point of disease-free survival (DFS), with data showing that at a median follow-up of 24 months (range, 2-64), cemiplimab reduced the risk of recurrence or death by 68% vs placebo (HR, 0.32; 95% CI, 0.20-0.51; P < .0001). In patients in the cemiplimab (n = 205) and placebo (n = 204) arms, any-grade adverse effects (AEs) occurred in 91% vs 89% of patients, respectively. Of note, grade 3 or greater AEs were reported in 24% vs 14% of patients, respectively; AEs leading to treatment discontinuation were recorded in 10% and 1.5% of patients in the respective arms.

As of now, this is the most data available, although Patel anticipates more real data will be released in 2025, which could help identify the magnitude of benefit cemiplimab will provide for patients with high-risk CSCC, she concludes.