Efficacy and toxicity profile of first-line treatment for extensive-stage small cell lung cancer: A Bayesian network meta-analysis

Background: The efficacy and toxicity profiles for extensive-stage small cell lung cancer (ES-SCLC) are unclear. We aimed to address this gap through a Bayesian network meta-analysis. Methods: We performed network analysis from randomized controlled trials comparing these treatments: PD-(L)1 inhibitor, CTLA-4 inhibitor, CXCR inhibitor, PARP inhibitor, CDK inhibitor, chemotherapy, and their combinations. Pooled estimations of progression-free survival, overall survival, objective response rate, and toxicity (systematic and specific) were conducted within the Bayesian framework. Results: Twenty-five trials involving 9 strategies were included. In terms of progression-free survival and overall survival, PD-(L)1 inhibitor combined with cisplatin/carboplatin (P) and etoposide (E) shown the acknowledged superiority than other treatments. The addition of CTLA-4 inhibitor (ipilimumab) to EP had the highest response rate among these regimens, and the combination of chemotherapy (irinotecan) and cisplatin/carboplatin had the greatest probability of performing considerable systematic security. The secondary endpoint was specific adverse events, including vomiting, fatigue, thrombocytopenia, constipation, and decreased appetite; hence we depicted the specific toxicity profile of each regimen. In addition, we identified the differences between PD-1 inhibitors and PD-L1 inhibitors in prolonging overall survival time for the central nervous system (CNS)/liver metastases patients. Conclusions: EP combined with PD-(L)1 inhibitor followed by CTLA-4 inhibitors or anti-angiogenesis was the considerable treatment with considerable efficacy and safety for ES-SCLC. Each treatment has a unique specific toxicity profile, which needs more attention.