Adjuvant Immunotherapy for CSCC: KEYNOTE-630 Insights
# Adjuvant Immunotherapy Shows Promise in High-Risk Cutaneous Squamous Cell Carcinoma
The landscape of treating high-risk cutaneous squamous cell carcinoma (cSCC) is rapidly evolving, with adjuvant immunotherapy emerging as a significant area of interest. Recent clinical trial data, especially from KEYNOTE-630 and the C-POST trial, suggest that immunotherapy administered after surgery and radiation can dramatically reduce recurrence rates in patients with locally advanced disease. This has sparked considerable optimism for its potential integration into future standards of care.## Adjuvant Immunotherapy: reducing recurrence in High-Risk cSCC
For patients diagnosed with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) following surgery and radiation, the timing of adjuvant immunotherapy appears crucial. Early administration, ideally within the first couple of months post-treatment, is considered crucial for maximizing its benefit.
While the KEYNOTE-630 trial, which evaluated adjuvant pembrolizumab versus placebo in high-risk LA cSCC, did not initially demonstrate an overall survival (OS) benefit, this finding is tempered by the trial’s crossover arm. In this arm, a substantial number of patients who experienced recurrence in the placebo group afterward received PD-1 therapy, often with pembrolizumab or cemiplimab, and achieved significant responses.This crossover effect likely masked a potential OS advantage in the primary analysis.
Despite this, the aggregate data from KEYNOTE-630 and the C-POST trial strongly indicate that adjuvant immunotherapy is an effective treatment. It has shown a remarkable ability to reduce recurrence rates. The key unanswered question remains whether this reduction in recurrence will ultimately translate into a significant overall survival benefit. However, the observed efficacy in reducing recurrence, coupled with manageable morbidity in the right patient population, fuels hope that adjuvant immunotherapy will become a standard component of care for these patients.
## The Expanding Role of Immunotherapy in Nonmelanoma Skin Cancers
Beyond adjuvant therapy, there is considerable excitement surrounding the use of neoadjuvant immunotherapy for skin cancers. A notable trial involving cemiplimab demonstrated promising results,with a 50% pathologic complete response rate observed in 79 patients.
To further validate these findings, a large, confirmatory phase 3 trial, the NRG Oncology HN014 trial led by neil Gross, MD, FACS, is currently underway. This trial will compare neoadjuvant immunotherapy directly against the traditional surgery-first approach. Many centers across the US and Australia are participating, and the oncology community is optimistic that this trial will establish neoadjuvant immunotherapy as a new standard of care for eligible patients.
For patients who undergo surgery first followed by adjuvant radiation, the role of adjuvant immunotherapy is still being defined. Tho, based on the encouraging results from trials like C-POST and KEYNOTE-630, there is a strong expectation that adjuvant immunotherapy will be incorporated into future treatment guidelines for these patients.
### references:
1. Koyfman SA, Lee JH, Mortier L, et al. Phase 3 randomized trial (KEYNOTE-630) of adjuvant pembrolizumab (pembro) versus placebo (pbo) for high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) following surgery and radiation (RT). *J Clin Oncol*.2025;43(suppl 17):6000. doi:10.1200/JCO.2025.43.16_suppl.6000
2. Adjuvant Libtayo® (cemiplimab) considerably improves disease-free survival (DFS) after surgery in high-risk cutaneous squamous cell carcinoma (CSCC) in phase 3 trial. News release. Regeneron pharmaceuticals, Inc. January 13, 2025. accessed July 14, 2025. https://tinyurl.com/46b9f65k