Cemiplimab Prolongs Survival Compared With Historical Systemic Treatment Options in Advanced Cutaneous Squamous Cell Carcinoma

Clinical Summary:

• Design/Population: In the multicenter, retrospective TOSCA trial, researchers compared cemiplimab with historical systemic therapies in patients with locally advanced or metastatic cutaneous squamous cell carcinoma who were ineligible for curative surgery or radiotherapy. 
• Key Outcomes: Cemiplimab significantly prolonged overall and progression-free survival, reducing the risk of disease progression or death by 43%. Objective response was also significantly higher, with a greater proportion of patients achieving complete response. 
• Clinical Relevance: These real-world findings strengthen evidence supporting cemiplimab as standard systemic treatment option when curative surgery or radiotherapy is not an option.

Real-world findings from the TOSCA trial demonstrated that cemiplimab significantly improved overall and progression-free survival (PFS) compared with historical systemic options in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) ineligible for curative surgery or radiotherapy. 

“While most patients with cSCC have a favorable prognosis, 3%–5% of patients progress to advanced stages of the disease that cannot be treated by surgery or radiotherapy,” stated Caroline Robert, MD, Gustave Roussy and Paris Saclay University, Villejuif, France, and coauthors. “Cemiplimab, an anti-programmed cell death receptor-1 antibody, was approved by the FDA and EMA for patients with locally advanced cSCC ineligible for curative surgery/radiotherapy.” 

In this multicenter, noninterventional trial, researchers compared data from patients with locally advanced cSCC treated with cemiplimab through the French early access program between 2018 and 2019 with patients who received historical systemic therapies between 2013 and 2018. The primary end point was OS. Key secondary end points included PFS, duration of response, objective response rate (ORR), and safety. 

Overall, the real-world population included 280 patients, including 147 treated with cemiplimab and 133 treated with historical systemic therapy. The primary effectiveness analysis focused on a trial-like population of immunocompetent patients meeting early access program criteria, including 129 patients treated with cemiplimab and 70 treated with historical systemic therapies. 

 At analysis, media OS was 21.2 months in the cemiplimab arm and 9.8 months in the historical control arm (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.45 to 0.73; P < .0001). Median PFS was 13.7 month and 5.3 months, respectively (HR, 0.57; 95% CI, 0.43 to 0.76; P = .0001). 

The ORR was 56.6% in the cemiplimab arm and 32.6% in the historical control arm (P <.001). Complete responses occurred in 30.2% and 15.2% of patients, respectively, while partial responses occurred in 26.4% and 17.4% of patients, respectively. 

Median duration of response was 21.7 months in the cemiplimab arm and 5.3 months in the historical control arm. However, the between-group difference in duration of response was not statistically significant (HR, 0.58; 95% CI, 0.3 to 1.12; P = .1033). 

Safety was evaluated in the broader real-world population. Adverse drug reactions were reported in 27% of patients in the cemiplimab arm and 33% of patients in the historical control arm. Adverse drug reactions led to permanent treatment discontinuation in 19% and 23% of patients, respectively. 

Adverse drug reactions resulting in death occurred in 3% of patients in the cemiplimab arm and 4% of patients in the historical control arm. No new safety concerns were reported. 

“Results underscore the efficacy of cemiplimab, solidifying its position as the standard of care for patients not eligible for curative surgery or radiation,” concluded Dr Robert et al. 

Source:

Robert C, Gérard E, Lanoy E, et al. Cemiplimab versus historical systemic treatments for locally advanced or metastatic cutaneous squamous cell carcinomas: Results from the French study TOSCA. Eur J Cancer. Published online: May 2, 2026. doi: 10.1016/j.ejca.2026.116596