Citation
Gross ND, Miller DM, Khushalani NI, et al. Phase II study of neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma: final analysis. J Clin Oncol. Published online October 24, 2026. doi:10.1200/JCO-26-02166.
Overview
Neoadjuvant immunotherapy may improve the management of resectable cutaneous squamous cell carcinoma (CSCC) by inducing tumor regression before surgery and potentially reducing the need for additional local treatment. Whether the encouraging pathologic responses seen in early reports translate into durable disease control has been a central question.
This final analysis reports long-term outcomes from a multicenter, single-arm phase II study of 79 patients with resectable stage II–IV (M0) CSCC. Patients received up to four doses of cemiplimab before curative-intent surgery. Postoperative treatment with radiation, cemiplimab, or observation was determined by investigators. At a median follow-up of 54 months, the study evaluated event-free survival, disease-free survival, overall survival, safety, and exploratory immune biomarkers.
After more than four years of median follow-up, no additional CSCC recurrences were observed beyond those reported in the earlier analysis. Importantly, none of the 40 patients who achieved a pathologic complete response experienced disease recurrence, despite 24 of those 40 patients receiving no additional treatment after surgery.
Long-Term Outcomes
Estimated overall survival at 54 months was 79.4%, and estimated disease-free survival at 48 months among the 70 patients who underwent surgery was 81.9%. Sixteen event-free survival events occurred in the full cohort: three disease recurrences, two instances of progression precluding surgery, and 11 deaths without recurrence.
The five additional event-free survival events since the 19-month follow-up were all deaths without CSCC recurrence. No new grade 3 or higher treatment-emergent adverse events or new safety signals were reported.
Clinical Interpretation
- Pathologic response remained associated with favorable long-term outcomes: estimated 54-month event-free survival was 81.5% after pathologic complete response and 88.9% after major pathologic response.
- None of the 40 patients with pathologic complete response developed recurrent CSCC; 24 (60%) received observation without further postoperative treatment.
- Exploratory blood-based analyses showed increased markers of T-cell activation and proliferation during treatment among patients achieving complete or major pathologic response.
- The findings strengthen the rationale for studying response-adapted surgery and postoperative treatment, but the single-arm design cannot establish whether treatment de-escalation is equivalent to standard management.
- Neoadjuvant cemiplimab for resectable CSCC remains investigational; this report should not be interpreted as establishing a new approved neoadjuvant standard.
Study History
The final report extends the initial 2022 publication demonstrating a 51% pathologic complete response rate and the 2023 follow-up describing early survival outcomes. The present analysis adds a median 54 months of follow-up, allowing a longer view of response durability and late safety events.
Authors
Neil D. Gross, David M. Miller, Nikhil I. Khushalani, Vasu Divi, Emily S. Ruiz, Evan J. Lipson, Friedegund Meier, Yungpo Bernard Su, Paul L. Swiecicki, Jennifer Atlas, Jessica L. Geiger, Axel Hauschild, Jennifer Hsing Choe, Brett G. M. Hughes, Annette M. Lim, Renata Ferrarotto, Bei Wang, Weiwei Tao, Laura Brennan, Suk-Young Yoo, Frank Seebach, Israel Lowy, Melissa Mathias, Hyunsil Han, Matthew G. Fury, and Danny Rischin.