Citation
Miller DM, Merkin RD, Kaufman HL, Gupta SG, Wolkow N, Adelaja A, Sullivan RJ, Patel C, Sorrentino A, Cohen S, Cimoch C, Emerick KS. Frontline immunotherapy with response-guided subsequent treatment (FIRST) in cutaneous squamous cell carcinoma: a Bayesian causal analysis of dose intensity, early benefit, and treatment de-escalation. J Immunother Cancer. 2026;14(7):e015029. doi:10.1136/jitc-2026-015029.
Overview
Immune checkpoint inhibitors can produce substantial responses in resectable and locally advanced cutaneous squamous cell carcinoma, but the optimal duration of treatment—and the value of routine surgery or radiation after a deep response—remain uncertain.
FIRST evaluated 189 patients treated with immune checkpoint inhibitors as part of management for resectable, borderline-resectable, locally advanced, or limited metastatic CSCC. The study used Bayesian regression, directed acyclic graphs, and a prespecified landmark analysis to examine how dose intensity, early response, and subsequent treatment related to clinical outcomes.
Durable disease control frequently occurred after limited immunotherapy exposure. Although additional doses may provide modest benefit, the observed gains appeared concentrated early, with uncertain incremental value beyond two doses.
Clinical interpretation
- Nearly half of patients received two or fewer doses of immunotherapy.
- Clinical complete responders often maintained durable control without routine surgical consolidation.
- The strongest evidence for incremental benefit appeared between the first and second doses.
- Additional treatment beyond two doses may help some patients, but the magnitude of downstream benefit remains uncertain.
- The findings support a response-guided treatment framework rather than a fixed-duration neoadjuvant model.
Authors
David M. Miller, Ross D. Merkin, Howard L. Kaufman, Sameer G. Gupta, Natalie Wolkow, Adewunmi Adelaja, Ryan J. Sullivan, Chirayu Patel, Alexandra Sorrentino, Sonia Cohen, Christine Cimoch, and Kevin S. Emerick.