Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy as first-line treatment for extensive-stage small cell lung cancer: a meta-analysis based on mixed-effect models

Jianqing Zheng; Yujie Deng; Bifen Huang; Xiaohui Chen

doi:10.3389/fmed.2023.1198950

Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy as first-line treatment for extensive-stage small cell lung cancer: a meta-analysis based on mixed-effect models

Front Med (Lausanne). 2023 Jul 31:10:1198950. doi: 10.3389/fmed.2023.1198950. eCollection 2023.

Authors

Jianqing Zheng^#¹, Yujie Deng^#², Bifen Huang³, Xiaohui Chen^{4

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Affiliations

¹ Department of Radiation Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
² Department of Medical Oncology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
³ Department of Obstetrics and Gynecology, Quanzhou Medical College People's Hospital Affiliated, Quanzhou, Fujian, China.
⁴ Department of Thoracic Surgery, Fujian Cancer Hospital, Clinical Oncology School of Fujian Medical University, Fuzhou, Fujian, China.
⁵ The Graduate School of Fujian Medical University, Fuzhou, China.
⁶ Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, China.

^# Contributed equally.

Abstract

Background: Extensive-stage small cell lung cancer (ES-SCLC) is a highly invasive and fatal disease with limited therapeutic options and poor prognosis. Our study aims to systematically evaluate the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy (ICIs+ChT) vs. chemotherapy alone (ChT) in the first-line treatment of ES-SCLC.

Methods: A literature search was performed for randomized controlled trials (RCTs) related to "ICIs+ChT" vs. "ChT" in the first-line treatment of ES-SCLC in PubMed, Cochrane Library, Embase, CNKI, and other databases. RevMan 5.4 software was used to perform meta-analyses with hazard ratio (HR) and relative risk (RR). SAS 9.4 software was applied to conduct a mixed-effect model meta-analysis of the survival outcomes and draw survival curves.

Results: A total of 2,638 patients with ES-SCLC from 6 RCTs were included, of which 1,341 patients received "ICIs+ChT" and 1,297 received ChT. Based on the meta-analysis results provided by the mixed-effect model, patients receiving the "ICIs+ChT" regimen had a significantly longer overall survival (OS, HR = 0.800, 95% CI = 0.731-0.876, P < 0.001) and progression-free survival (PFS, HR = 0.815, 95% CI = 0.757-0.878, P <0.001) in comparison to those receiving ChT only. Compared with ChT, "ICIs+ChT" did neither improve the objective response rate (ORR, RR = 1.06, 95% CI = 1.00-1.12, P = 0.06) nor did it improve the disease control rate (DCR, RR = 0.97, 95% CI = 0.92-1.03, P = 0.35). Although the incidence of grade 3 to 5 treatment-related adverse events (trAEs) in the "ICIs+ChT" subgroup did not increase (RR = 1.16, 95% CI = 0.97-1.39, P = 0.11), the incidence of grade 3 to 5 immune-related adverse events (irAEs) increased significantly (RR = 4.29, 95% CI = 1.73-10.61, P < 0.00001).

Conclusion: ICIs+ChT regimen could significantly prolong OS and PFS in patients with ES-SCLC compared with ChT alone. Although the incidence of irAEs in "ICIs+ChT" is higher than that in the "ChT" subgroup, the incidence of trAEs is similar within the two subgroups. ICIs combined with chemotherapy demonstrated a good choice as first-line treatment for ES-SCLC.

Systematic review registration: PROSPERO, identifier: CRD42022348496.

Keywords: chemotherapy; extensive-stage small cell lung cancer; first-line treatment; immune checkpoint inhibitors; programmed death-ligand 1.

Publication types

Systematic Review

Grants and funding

This study was supported in part by Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant No. 2020Y9036 to XC), the Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare (to XC), the National Clinical Key Specialty Construction Program (Grant No. 2021), the Fujian Provincial Clinical Research Center for Cancer Radiotherapy and Immunotherapy (Grant No. 2020Y2012), Fujian Provincial Natural and Scientific Foundation (Grant No: 2023J011255 to XC), the Fujian Provincial Health Technology Project (Youth Scientific Research Project, 2019-1-50 to JZ), the Nursery Fund Project of the Second Affiliated Hospital of Fujian Medical University (Grant No: 2021MP05 to JZ), and Fujian Education and Research Grants for Young and Middle-aged Teachers (Grant No: JAT220083 to YD).