Efficacy and safety of first-line immune checkpoint inhibitors combined with chemotherapy for extensive-stage small cell lung cancer: A network meta-analysis

Abstract

The efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) remains unevaluated, and there are no reports to directly compare the efficacy and safety among different immunotherapy (especially adebrelimab and surplulimab). Suitable phase III randomized controlled trials with two or more different arms were included. Independent reviewers screened and extracted relevant data and disagreements were resolved through consensus. Fixed-effect consistency models were used to calculate the overall survival (OS), progression-free survival (PFS), objective response rate, adverse events ≥ 3, and safety outcomes in the clinically relevant subgroups. In this network meta-analysis, six randomized controlled clinical trials (CAPSTONE-1, ASTRUM-005, CASPIAN, IMpower133, KEYNOTE-604, and an ipilimumab + chemotherapy trial) with totaling 3662 patients were involved. Compared to chemotherapy, immune checkpoint inhibitors plus chemotherapy present higher possibilities to bring about better OS and PFS. Serplulimab + chemotherapy significantly showed a better survival profit in comparison with ipilimumab + chemotherapy (0.67; 0.50-0.90). Compared with chemotherapy, adebrelimab + chemotherapy (0.72; 0,58-0.90), atezolizumab + chemotherapy (0.76; 0.60-0.96) durvalumab + chemotherapy (0.75; 0.62-0.91), and serplulimab + chemotherapy (0.63;0.49-0.82) all presented significantly better overall survival. In terms of progression-free survival, serplulimab + chemotherapy showed better efficacy in comparison with adebrelimab + chemotherapy (0.72; 0,53-0.97), atezolizumab + chemotherapy (0.62; 0.46-0.84), durvalumab + chemotherapy (0.60; 0.45-0.80). Compared with chemotherapy, adebrelimab + chemotherapy (0.67; 0.54-0.83) and serplulimab + chemotherapy (0.48; 0.48-0.86) all presented significantly better PFS. Immunotherapy plus chemotherapy had similar probabilities to cause adverse events of grade ≥ 3. In comparison with chemotherapy, immune checkpoint inhibitors plus chemotherapy were likely to be more suitable for the first-line treatment of ES-SCLC. According to our analysis, serplulimab plus chemotherapy and adebrelimab plus chemotherapy present higher possibilities to show better efficacy and safety, however, the level of evidence of this type of comparison is limited.

Keywords: Adebrelimab; Extensive-stage small cell lung cancer; Immune checkpoint inhibitors; Network meta-analysis; Serplulimab.