Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis

• Published in: Current oncology (Toronto) Vol. 29; no. 12; pp. 9046 - 9065
• Main Authors: Sathiyapalan, Arani, Febbraro, Michela, Pond, Gregory R, Ellis, Peter M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-11-2022; MDPI
• Subjects: Cancer; chemo-immunotherapy; Chemotherapy; Comparative analysis; Development and progression; extensive stage; Humans; Immunotherapy; Immunotherapy - methods; Ipilimumab; Lung cancer, Small cell; Lung Neoplasms - pathology; Progression-Free Survival; Quality of Life; Randomized Controlled Trials as Topic; SCLC; Small Cell Lung Carcinoma - drug therapy; Systematic Review; SCLC; chemo-immunotherapy; extensive stage; chemotherapy; immunotherapy
• ISSN: 1718-7729; 1198-0052; 1718-7729
• DOI: 10.3390/curroncol29120709

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with early metastatic potential. The standard-of-care treatment has not changed in years. Recent studies report improved progression-free survival (PFS) and overall survival (OS) with combined ICI and chemotherapy in ES-SCLC. We conducted a systematic review and meta-analysis to assess the magnitude of survival benefits. We searched MEDLINE, EMBASE, and Cochrane between 1 January 2010 and 15 July 2022 and conference proceedings from 2018 to 2022, for randomised controlled trials, evaluating chemo-ICI compared with platinum-doublet chemotherapy in untreated ES-SCLC. Outcomes assessed were PFS, OS, objective response rate (ORR), duration of response (DoR), toxicity, and health-related quality of life (HRQoL). The search identified 8061 studies, with 8 (56 publications) included in the final analysis. PFS and OS were significantly improved for patients randomised to chemo-ICI (PFS hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.70-0.80) and (OS HR 0.79, 95% CI 0.73-0.85). Subgroup analysis demonstrated a differential effect between PD-1/PD-L1 and CTLA-4 inhibitors. There was no difference in ORR and DoR. All-grade adverse events (RR 1.06, 95% CI 1.00-1.12) were similar. The addition of ICI to chemotherapy in untreated ES-SCLC results in a 22% risk reduction in death, and a 25% risk reduction in disease progression with a minimal increase in toxicity. These improvements are modest but represent progress beyond the standard of care.