Background: Cutaneous 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.
Methods: We 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.
Results: Overall, 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.
Conclusion: ICB is superior to other systemic treatments and sets a novel survival benchmark for advanced cutaneous squamous cell carcinoma.
Keywords: Cutaneous neoplasm; Cutaneous squamous cell carcinoma; Immune checkpoint blockade; Indirect comparison; Individual patient data; Overall survival; PD-1 therapy; Progression-free survival; Skin cancer.
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