Myelopreservation effect of trilaciclib in extensive-stage small cell lung cancer (ES-SCLC): a systematic review and meta-analysis with trial sequential analysis of randomized clinical trials

曲拉西利在广泛期小细胞肺癌(ES-SCLC)中的骨髓保护作用:一项系统评价和荟萃分析,以及随机临床试验的序贯分析

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Abstract

BACKGROUND: Small cell lung cancer (SCLC) patients undergoing chemotherapy often suffer from myelosuppression, which not only increases disease burden but also significantly impairs quality of life. A novel medication, trilaciclib, has been designed to mitigate myelosuppression and protect patients from its debilitating effects. Although trilaciclib has shown promising myeloprotection ability, researchers are seeking more evidence to gain substantial insights into its efficacy and safety profile, given the limited trial results and small sample sizes. Therefore, this study pools the efficacy and safety results of existing randomized controlled trials (RCTs) through meta-analysis and assesses the reliability of findings using trial sequential analysis (TSA). METHODS: Studies were searched in databases including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. Only RCTs with extensive-stage SCLC (ES-SCLC) patients receiving trilaciclib were included, with placebo as the comparator group. Risk of Bias 2 tools were applied to evaluate the risk of bias of included studies. Meta-analysis was conducted for result synthesis with TSA to assess the robustness of results. RESULTS: With predetermined search terms, a total of 135 studies and trials were screened, and eventually four trials were included in analysis with low risks of bias. Of the total 356 randomized patients from four trials, 195 received trilaciclib and 161 received placebo. The results indicated that trilaciclib could significantly reduce the occurrence of severe neutropenia (SN) [odds ratio (OR): 0.08; 95% confidence interval (CI): 0.04 to 0.15], shorten the duration of SN (DSN) in cycle 1 [mean difference (MD): -3.19; 95% CI: -3.96 to -2.42] and reduce the occurrence of febrile neutropenia (FN) (OR: 0.22; 95% CI: 0.08 to 0.59). CONCLUSIONS: Our meta-analysis with TSA provided robust evidence that trilaciclib could significantly protect ES-SCLC patients receiving chemotherapies from myelosuppression, thereby enabling more consistent treatment administration and potentially enhancing clinical outcomes. However, more studies are necessary to clarify indirect outcomes.

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