Cemiplimab versus historical systemic treatments for locally advanced or metastatic cutaneous squamous cell carcinomas: Results from the French study TOSCA

BACKGROUND: Cemiplimab an anti-programmed cell death receptor-1 antibody, was approved by the FDA and EMA for patients with locally advanced cutaneous squamous cell carcinoma (laCSCC) ineligible for curative surgery/radiotherapy or with metastatic (m) CSCC. TOSCA study evaluated the real-world effectiveness and safety of cemiplimab compared to historical systemic therapies (HSTs). METHODS: TOSCA (NCT05302297) was a large French retrospective, multicenter study comparing patient with la/mCSCC treated with cemiplimab via the early access program (EAP, 2018-2019) or HST (2013-2018). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), and safety. Effectiveness analysis using inverse probability weighting included a trial-like cohort of only immunocompetent patients meeting the EAP criteria to emulate a randomized clinical trial; safety analysis included all real-life patients. FINDINGS: The study included 280 real-life patients (cemiplimab: n = 147; HST: n = 133). The primary effectiveness analysis included a trial-like cohort (cemiplimab: n = 129; HST: n = 70; median age: 81 and 78 years, respectively). Median follow-up was 20 and 10 months in the cemiplimab and HST arms, respectively; median OS was 21.2 and 9.8 months, respectively (HR 95% CI: 0.57 [0.45-0.73]; P < 0.0001); median PFS was 13.7 and 5.3 months, respectively (HR [95% CI]: 0.57 [0.43-0.76]; P = 0.0001). Adverse drug reactions occurred in 27% of cemiplimab patients and 33% of HST patients. INTERPRETATION: TOSCA demonstrated better survival and response outcomes for cemiplimab versus HST in la/mCSCC; emphasizing, the importance of this retrospective studie in the absence of standard comparative trials.