Efficacy and safety of poly ADP-ribose polymerase inhibitors (PARPis) in extensive-stage small-cell lung cancer (ES-SCLC) treatment: a systematic review and meta-analysis

聚ADP核糖聚合酶抑制剂(PARPis)治疗广泛期小细胞肺癌(ES-SCLC)的疗效和安全性:系统评价和荟萃分析

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Abstract

BACKGROUND: Given the high invasiveness of extensive-stage small-cell lung cancer (ES-SCLC), the limited treatment options available, and the definite efficacy of poly ADP-ribose polymerase inhibitors (PARPis) in the treatment of diverse cancers, such as metastatic castration-resistant prostate cancer, recurrent ovarian cancer, and advanced breast cancer, we performed a meta-analysis to evaluate the efficacy and toxicity of PARPis in the treatment of ES-SCLC. METHODS: A systematic literature search of online databases was conducted to retrieve relevant articles published before March 2025. Six articles on randomized controlled trials (RCTs) involving 924 patients were included in the meta-analysis. The relative risk (RR)/odds ratio (OR) data were extracted from the RCTs as the research objects to conduct an integrated analysis via RevMan5.4. RESULTS: The meta-analysis illustrated that PARPis significantly improved the objective response rate (ORR) [OR =2.03, 95% confidence interval (CI): 1.26-3.28] and progression-free survival (PFS) [hazard ratio (HR) =0.72, 95% CI: 0.63-0.81] of the ES-SCLC patients between the included 6 RCTS, especially those with SLFN-11 positive (+) expression (HR =0.65, 95% CI: 0.51-0.82), but it did not result in any overall survival (OS) benefit. Additionally, the application of PARPis resulted in higher rates of adverse events (AEs), including anemia, leukopenia, thrombocytopenia, vomiting, fatigue, and nausea, but these AEs were not life-threatening. CONCLUSIONS: Our findings confirmed that PARPis represent an effective treatment option for ES-SCLC patients, especially those with SLFN-11+ expression. Our meta-analysis revealed no apparent increase in OS in these patients; however, this might be due to the lack of sufficient data in the clinical trials; thus, more extensive studies with longer follow-up periods need to be conducted.

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