Sintilimab plus chemotherapy for first-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer: network meta-analysis

Aim: This systematic literature review and network meta-analysis evaluated the efficacy and safety of sintilimab + pemetrexed + platinum versus US FDA-approved/National Comprehensive Cancer Network-recommended immune checkpoint inhibitor (ICI) combination therapies for untreated advanced/metastatic non-squamous non-small-cell lung cancer without EGFR/ALK aberrations. Methods: Bayesian network meta-analysis was the base-case analysis and included assessment of fixed and random effects, and independent and simultaneous models, adjusting for baseline risk (placebo response). Chemotherapy was the common comparator. Results: Sintilimab + pemetrexed + platinum was associated with significantly longer progression-free survival than atezolizumab + platinum + nab-paclitaxel (hazard ratio [HR]: 0.57; 95% credible interval [CrI]: 0.40-0.82) and nivolumab + ipilimumab + pemetrexed + platinum (HR: 0.66; 95% CrI: 0.48-0.92). Sintilimab + pemetrexed + platinum and pembrolizumab + pemetrexed + platinum showed comparable progression-free survival (HR: 0.96; 95% CrI: 0.71-1.30). There was no significant difference in overall survival (HR range: 0.61-0.81) or overall response rates (odds ratio [OR] range: 0.29-0.75) between sintilimab + pemetrexed + platinum and the other ICI combinations. The incidence of high-grade adverse events was higher with sintilimab + pemetrexed + platinum than with nivolumab + ipilimumab (OR: 0.46; 95% CrI: 0.33-0.64) or without chemotherapy (OR: 0.25; 95% CrI: 0.19-0.34), with no significant difference between sintilimab + pemetrexed + platinum and the other ICI combinations. Conclusion: Sintilimab + pemetrexed + platinum showed comparable efficacy and safety versus US standard-of-care first-line ICI combinations for advanced/metastatic non-squamous non-small-cell lung cancer.