The benefit and risk of adding immunotherapy to chemoradiotherapy as the first-line treatment for limited-stage small cell lung cancer: a meta-analysis of randomized controlled trials

Limited-stage small cell lung cancer (LS-SCLC) remains a highly aggressive malignancy with limited long-term survival despite standard chemoradiotherapy (CRT). Recently, immunotherapy has emerged as a promising adjunct to CRT, but its efficacy and safety in the first-line treatment of LS-SCLC remain uncertain. This meta-analysis of randomized controlled trials (RCTs) aimed to systematically evaluate the clinical benefits and risks of combining immunotherapy with CRT (ICRT) versus CRT alone in patients with LS-SCLC. RCTs comparing ICRT and CRT as initial therapy for LS-SCLC were retrieved from 6 databases. Data on overall survival (OS), progression-free survival (PFS), responses, and adverse events (AEs) were extracted. Pooled hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models, depending on heterogeneity. A total of 6 RCTs comprising 1036 patients were included. Compared with CRT alone, ICRT significantly improved OS (HR: 0.80 [0.67, 0.96], P = 0.02) and PFS (HR: 0.78 [0.65, 0.94], P = 0.008). Subgroup analyses of OS and PFS demonstrated that time from end of concurrent CRT to randomization < 14 day, and platinum type - carboplatin were favorable factors for ICRT group. The objective response rate (ORR), and disease control rate (DCR) were similar between the two group. However, the ICRT therapy was associated with more total/ grade 3–5 immune-related AEs (irAEs). The most common irAEs were hypothyroidism (13.64%), and pneumonitis (11.74%) in the ICRT group. First-line ICRT significantly improves survival outcomes in patients with LS-SCLC compared to CRT alone, albeit with a higher risk of irAEs. CRD420251076364