Indirect comparison of sintilimab and other PD-L1 inhibitors for first-line treatment of non-squamous non-small-cell lung cancer

Objective: To evaluate sintilimab compared with other PD-L1 inhibitors in combination with platinumbased doublet chemotherapy as the first-line treatment of non-squamous non-small-cell lung cancer. Methods: A frequentist meta-analysis was used to compare outcomes, including progression-free survival, overall survival, objective response rate, time to response and safety profile. Results: The sintilimab combination arm had progression-free survival comparable to that of the pembrolizumab combination arm (hazard ratio [HR] - 1.00; 95% CI: 0.71, 1.41), the atezolizumab combination arm (HR: 0.81; 95% CI: 0.59, 1.10), the tislelizumab combination arm (HR: 0.75; 95% CI: 0.48, 1.16), the camrelizumab combination arm (HR: 0.80; 95% CI: 0.54, 1.20) and the nivolumab combination arm (HR: 0.72; 95% CI: 0.51, 1.02). Any grade or grade >= 3 adverse event was comparable between PD-L1 inhibitors. Conclusion: Sintilimab showed a comparable efficacy and safety profile when compared with other PD-L1 inhibitors combined with platinum-based doublet chemotherapy as the first-line treatment of locally advanced or metastatic non-squamous non-small-cell lung cancer. Plain language summary: Lung cancer is the most diagnosed cancer and the leading cause of cancerrelated mortality in China. Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers, of which non-squamous NSCLC (nsqNSCLC) is the most frequent histologically, occupying 70% of NSCLC. Six different PD-L1 inhibitors (sintilimab, pembrolizumab, camrelizumab, atezolizumab, tislelizumab and nivolumab) in combination with chemotherapy have been approved as the first-line treatment of advanced/metastatic nsqNSCLC patients in China. Since there is no direct evidence of comparable efficacy and safety due to a lack of head-to-head trials among the PD-L1 inhibitors, an indirect comparison was conducted to evaluate sintilimab compared with other PD-L1 inhibitors in combination with platinum-based doublet chemotherapy. The results showed that sintilimab combined with platinum-based doublet chemotherapy showed progression-free survival, overall survival, objective response rate, time to response and safety profile comparable to other PD-L1 inhibitors in combination with platinum-based doublet chemotherapy as the first-line treatment of locally advanced or metastatic nsqNSCLC patients.