Comparative efficacy analysis identifies immune checkpoint blockade as a new survival benchmark in advanced cutaneous squamous cell carcinoma

Abstract

BackgroundCutaneous squamous cell carcinoma is a common type of skin cancer that may progress to locally advanced or metastatic disease. Both disease stages are managed by a variety of treatment options, including immune checkpoint blockade (ICB), targeted therapy to epidermal growth factor, chemotherapy or treatment combinations. However, the comparative efficacy of such treatments is unclear. MethodsWe performed a systematic literature search of Medline, Embase and Central to identify eligible studies reporting Kaplan–Meier curves or individual patient data for overall survival (OS) or progression-free survival (PFS). Kaplan–Meier curves were digitised using the “‘WebPlotDigitizer” program. Individual patient data was subsequently remodelled and pooled for distinct treatment groups. ResultsOverall, 22 independent studies were included of which n = 927 patients were evaluable for PFS and n = 1054 for OS. ICB showed the highest median PFS (mPFS 9.9 months (95% CI: 8.1–19.9)) and median OS (mOS not reached (95% CI: 31.5 months-not reached)) compared to chemotherapy (mPFS 3.0 months (95% CI: 2.2–4.8), mOS 12.6 months (95% CI: 9.6–15.8)), targeted therapy to epidermal growth factor (mPFS 4.9 months (95% CI: 4.4–5.6), mOS 12.7 months (95% CI: 11.9–14.9)) and combination therapies without ICB (mPFS 9.1 months (95% CI: 8.0–12.1), mOS 18.1 months (95% CI: 16.3–22.8)). The survival benchmark with ICB after 26 months for metastatic squamous cell carcinoma was 70.8% (95% CI: 61.5%–81.5%) versus 37.9% (95% CI: 29.5%–48.8%) for the combination group and 17.1% (95% CI: 9.5%–30.8%) for chemotherapy. ConclusionICB is superior to other systemic treatments and sets a novel survival benchmark for advanced cutaneous squamous cell carcinoma.