While immune checkpoint inhibitors (ICIs) have been approved for treating small-cell lung cancer (SCLC), the efficacy and safety profile of ICIs for relapsed SCLC is the subject of ongoing investigation. In a meta-analysis published in the Journal of Clinical Pharmacy and Therapeutics, researchers evaluated the efficacy and safety of ICIs in the treatment of relapsed SCLC patients. The scientists utilized various databases, including PubMed, Embase, and the Cochrane library, which they systematically searched to retrieve potential eligible studies from the establishment of the database to May 2021.

The primary outcomes were survival, treatment responses, and safety. Randomized, controlled trials and real-world studies that met the inclusion criteria were included. The RevMan 5.4 and R software were utilized for this meta-analysis. The researchers included a total of eight articles involving 653 patients.

In general, the meta-analyses results revealed that the overall response rate (objective response rate [ORR]) of the ICIs group was 0.12 (95% confidence interval [CI]: 0.07-0.18). The median overall survival was 7.97 (95% CI: 5.94-9.47) months, while the progression-free survival was 1.70 (95% CI: 1.40-2.28) months. Although chemotherapy demonstrated a favorable ORR (odds ratio [OR] = 0.74; 95% CI: 0.39-1.41; P = .36) and a significantly better disease control rate (OR = 0.28; 95% CI: 0.11-0.70; P = 0.007), patients treated with ICIs had a diminished risk of mortality (hazard ratio = 0.87; 95% CI: 0.73-1.03; P = .10). With regards to adverse events (AEs), the rates of any AEs and ≥grade 3 AEs were 0.56 (95% CI: 0.52-0.60) and 0.13 (95%CI: 0.06-0.20), respectively.

The authors noted that the study had several limitations, including (1) the sample sizes of the included studies were small, especially after restricting to RCTs and subgroup analysis that may underestimate the overall effect of ICIs on treating relapsed SCLC. (2) The baseline and clinical characteristics varied across the included studies and the types of antiprogrammed cell death protein (PD-1/PD-L1) agents were different among the included studies and consisted of nivolumab, pembrolizumab, and atezolizumab. The researchers indicated that the first-line treatment regimen and details may also be different and, as a result, this may introduce heterogeneity and heighten the risk of selection bias. In this study, the random-effect model was utilized to diminish potential heterogeneity and to combine the data and evaluate the overall effect. (3) Finally, there were few studies included in this study, and they were mostly single-arm trials. Therefore, further investigation is required to reduce the above limitations.

The researchers concluded that for relapsed SCLC patients, the administration of ICIs resulted in a comparable survival outcome and acceptable safety compared with chemotherapy. They also noted that further studies are necessary to explore potential biomarkers for relapsed SCLC patients who may benefit from immunotherapy.

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