多聚二磷酸腺苷核糖聚合酶抑制剂治疗BRCA突变乳腺癌疗效和安全性的Meta分析

Meta-analysis of clinical efficacy and safety of poly(ADP-ribose)polymerase inhibitors in treatment of BRCA mutated breast cancer

目的系统性评价多聚二磷酸腺苷核糖聚合酶(PARP)抑制剂治疗乳腺癌易感基因(BRCA)突变乳腺癌的疗效和安全性。方法检索Pub Med、Embase、Cochrane Library、CNKI、VIP、Sino Med和万方数据库中从2010年1月1日至2022年8月1日所有相关的随机对照临床试验。主要的研究终点是无进展生存期(PFS),次要研究终点是总生存期、客观缓解率和不良事件。结果最终纳入4项符合条件的随机对照临床研究,共纳入1438例患者。Meta分析的结果显示,含有PARP抑制剂的治疗方案显著改善了胚系BRCA突变转移或局部晚期乳腺癌患者的无进展生存期(P<0.00001,HR=0.64,95%CI:0.56~0.74)和客观缓解率(P=0.05,RR=1.54,95%CI:1.01~2.36),然而并没有明显改善总生存期(P=0.06,HR=0.86,95%CI:0.73~1.01)。3级及以上不良事件的发生率之间差异无统计学意义(P=0.39,RR=0.93,95%CI:0.78~1.10)。结论PARP抑制剂可以延长胚系BRCA突变转移或局部晚期乳腺癌患者群体的无进展生存期和客观缓解率,但无法显著改善总生存期,同时不会增加3级以上不良事件发生率。这些发现还需要更多临床研究进一步验证。

AIM To systematically assess the efficacy and safety of poly(ADP-ribose)polymerase(PARP)inhibitors for breast cancer patients with breast cancer susceptibility gene(BRCA)mutations.METHODS All randomized controlled trials(RCTs)of PubMed,Embase,Cochrane Library,CNKI,VIP,SinoMed and Wanfang Data from January 1,2010 to August 1,2022 were searched.RESULTS Four eligible RCTs were included with a total of 1438 patients.The main outcome of included studies was progression-free survival(PFS)and the secondary outcomes were overall survival(OS),objective response rate(ORR)and adverse drug reactions.Meta-analysis revealed that PARP inhibitors significantly improved the PFS(P<0.00001,HR=0.64,95%CI:0.56-0.74)and ORR(P=0.05,RR=1.54,95%CI:1.01-2.36)of metastatic or locally advanced breast cancer patients with germline BRCA mutations.However,PARP regimens did not significantly improve the overall survival(OS)of this patient population(P=0.06,HR=0.86,95%CI:0.73-1.01).The incidence of adverse events of grade 3 and above was no difference between 2 groups(P=0.39,RR=0.93,95%CI:0.78-1.10).CONCLUSION PARP regimens can significantly improve PFS and ORR of metastatic or locally advanced breast cancer patients with germline BRCA mutations,but it fails to significantly prolong OS.At the same time,PARP regimens may not increase the occurrence of grade 3 and above adverse events.These findings should be verified according to more clinical evidence in the future.