Efficacy of PD-1/PD-L1 inhibitors in first-line treatment of extensive-stage small cell lung cancer: a network meta-analysis
10.3760/cma.j.cn115355-20240715-00354
- VernacularTitle:PD-1/PD-L1抑制剂联合化疗一线治疗广泛期小细胞肺癌效果的网状Meta分析
- Author:
Enhui WEN
1
;
Chuan GAO
;
Juanni DONG
;
Ying LI
Author Information
1. 西安医学院第一附属医院临床药学室，西安 710077
- Publication Type:Journal Article
- Keywords:
Lung neoplasms;
Immune checkpoint inhibitors;
Antineoplastic combined chemotherapy protocols;
Treatment outcome;
Meta-analysis;
Extensive-stage small-cell
- From:
Cancer Research and Clinic
2025;37(10):766-773
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of different programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:All randomized controlled trials (RCT) of PD-1/PD-L1 inhibitors for the first-line treatment of ES-SCLC from the establishment of the database to March 2025 were searched in CNKI database, Wanfang database, VIP Chinese Science and Technology Journal database, China Biomedical Literature Service System, PubMed database, Cochrane Library database and Embase database. Literatures were screened according to inclusion and exclusion criteria, and data were extracted. A network meta-analysis was performed using R 4.3.1 software to analyze the survival and safety of patients with ES-SCLC treated with PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy±placebo first-line treatment.Results:A total of 8 RCT involving 3 832 patients with ES-SCLC were included in this analysis. PD-1/PD-L1 inhibitors included pembrolizumab, serplulimab, toripalimab, tislelizumab, adebrelimab, durvalumab, atezolizumab and benmelstobart, and benmelstobart combined with anti-vascular targeted drug anlotinib; the chemotherapy regimen was etoposide combined with platinum-based drugs. Except for durvalumab combined with chemotherapy compared with chemotherapy alone, the control group of the rest was chemotherapy combined with placebo. The included study data were complete and the risk of bias was small, and there was no closed loop in the outcome measures, so the consistency model was uniformly used for analysis. The results of network meta-analysis showed that compared with the control group, PD-1/PD-L1 inhibitors combined with chemotherapy benefited the progression-free survival (PFS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in PFS ( HR = 0.32, 95% CI: 0.25-0.40, P < 0.05), and this regimen could benefit the PFS of patients more than other PD-1/PD-L1 inhibitors combined with chemotherapy and serplulimab combined with chemotherapy could benefit the PFS of patients more than pembrolizumab, toripalimab, adebrelimab, durvalumab, and atezolizumab combined with chemotherapy (all P < 0.05). The results of network meta-analysis showed that compared with the control group, all PD-1/PD-L1 inhibitors combined with chemotherapy benefited the overall survival (OS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in OS ( HR = 0.61, 95% CI: 0.47-0.79, P < 0.05), but there was no statistically significant difference in OS benefit between each PD-1/PD-L1 inhibitor combined with chemotherapy (all P > 0.05). Ranking of the efficacy of all interventions, the P-scores for PFS and OS were the highest for benmelstobart and anlotinib combined with chemotherapy, which were 0.99 and 0.89, respectively. The results of the network meta-analysis showed that, except for the higher risk of ≥ grade 3 adverse reactions in benmelstobart and anlotinib combined with chemotherapy group compared to the control group ( OR = 2.01, 95% CI: 1.09-3.73, P < 0.05), there was no statistically significant difference in the risk of ≥ grade 3 adverse reactions between the other PD-1/PD-L1 inhibitors combined with chemotherapy group and the control group, or between all PD-1/PD-L1 inhibitors combined with chemotherapy groups (all P > 0.05). Among all PD-1/PD-L1 inhibitors combined with chemotherapy regimens, the tislelizumab combined with chemotherapy regimen had the lowest incidence of ≥grade 3 adverse reactions, with a P-score of 0.70. Conclusions:For the first-line treatment of ES-SCLC patients, the combination of PD-1/PD-L1 inhibitors and chemotherapy regimen has better survival benefits than chemotherapy regimen. Among them, compared with other PD-1/PD-L1 inhibitors, benmelstobart and anlotinib may benefit patients' survival more, but its related adverse reactions should be noted.
