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聚腺苷二磷酸核糖聚合酶抑制剂联合化疗与单独化疗治疗三阴性乳腺癌患者的疗效比较:基于随机对照试验的系统评价和荟萃分析。

PARP inhibitor plus chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: a systematic review and meta-analysis based on randomized controlled trials.

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, China.

Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.

出版信息

Cancer Chemother Pharmacol. 2023 Mar;91(3):203-217. doi: 10.1007/s00280-023-04506-x. Epub 2023 Feb 2.

Abstract

BACKGROUND

Chemotherapy is the standard treatment for triple-negative breast cancer (TNBC). Whether the addition of PARP inhibitors improves treatment efficacy remains controversial clinically. Thus, we performed a meta-analysis to compare the efficacy and safety of combination treatment (PC) and chemotherapy alone (CA).

METHODS

Relevant studies were identified through searches of 7 databases. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

RESULTS

We screened 317 studies and included seven RCTs involving 2091 patients in the final analysis. PC tended to have better efficacy than CA according to PFS (HR [hazard ratio]: 0.83 [0.75, 0.93], p = 0.001), OS (HR: 0.89 [0.76,1.03], p = 0.11) and overall response rate (ORR) (RR [risk ratio]: 1.19 [0.97,1.46], p = 0.10). However, grade 3-5 AEs (RR: 1.50 [0.87,2.61], p = 0.15) were observed in the PC group. In the PC arm, the 10 most-reported grade 3-5 AEs were neutropenia (62.8%), anemia (28.5%), thrombocytopenia (26.4%), lymphopenia (19.05%), leukopenia (16.9%), fatigue (5%), heart failure (4.76%), lung infection (4.76%), thromboembolic events (4.76%) and ventricular tachycardia (4.76%). Similar results for pathological complete response (pCR), total AEs, rate of complete response (CR), stable disease (SD) and progressive disease (PD), breast conservation rate (BCR), and drug discontinuation (DD) rate were found between the two groups.

CONCLUSIONS

For TNBC treatment, the combination of PARP inhibitors and chemotherapy appears to be superior to chemotherapy alone with better antitumor efficacy. However, its higher rate of AEs needs to be taken seriously. More high-quality RCTs are needed to confirm these results.

摘要

背景

化疗是三阴性乳腺癌(TNBC)的标准治疗方法。PARP 抑制剂的加入是否能提高治疗效果在临床上仍存在争议。因此,我们进行了一项荟萃分析,比较联合治疗(PC)和单独化疗(CA)的疗效和安全性。

方法

通过 7 个数据库的检索,确定了相关研究。主要终点是无进展生存期(PFS)和总生存期(OS)。

结果

我们筛选了 317 项研究,最终纳入了 7 项 RCT 共 2091 名患者。根据 PFS(HR:0.83 [0.75,0.93],p=0.001)、OS(HR:0.89 [0.76,1.03],p=0.11)和总缓解率(ORR)(RR:1.19 [0.97,1.46],p=0.10),PC 组的疗效优于 CA 组。然而,在 PC 组观察到 3-5 级不良反应(RR:1.50 [0.87,2.61],p=0.15)的发生率更高。在 PC 组中,报告的 10 种最常见的 3-5 级不良反应是中性粒细胞减少症(62.8%)、贫血(28.5%)、血小板减少症(26.4%)、淋巴细胞减少症(19.05%)、白细胞减少症(16.9%)、乏力(5%)、心力衰竭(4.76%)、肺部感染(4.76%)、血栓栓塞事件(4.76%)和室性心动过速(4.76%)。两组间病理完全缓解(pCR)、总不良反应发生率、完全缓解率(CR)、稳定疾病(SD)和进展疾病(PD)、保乳率(BCR)和药物停药率的结果相似。

结论

对于 TNBC 的治疗,PARP 抑制剂联合化疗似乎优于单独化疗,具有更好的抗肿瘤疗效。然而,其更高的不良反应发生率需要引起重视。需要更多高质量的 RCT 来证实这些结果。

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