>首先，在多个恶性肿瘤的80多项临床试验中评估了将PARP抑制剂与化疗联合应用的作用，其依据是PARP抑制剂能够增强化疗的有效性，无论肿瘤是否具有DNA修复通路的基础性破坏。因此，尽管在维持治疗中使用同源重组缺陷来决定使用PARP抑制剂，大多数联合治疗试验仍然在没有生物标志物选择的患者中进行。一个有待解决的问题是，是否需要生物标志物来识别对联合PARP抑制剂和化疗有响应的患者。通过系统文献回顾，我们找到了与单独化疗相比，使用PARP抑制剂与化疗联合治疗的研究，其中包括DNA修复功能的生物标志物（BRCA1、BRCA2、同源重组缺陷测试、ATM、ERCC1、SFLN11）。使用通用逆方差法、固定效应模型或随机效应模型，对风险比进行了元分析。我们还对生物标志物选择和恶性肿瘤类型进行了亚组分析。符合纳入标准的有9项研究，包括2547名患者。进展无病生存期（PFS）在具有DNA修复生物标志物的患者中显著改善（HR：0.57，95% CI：0.48-0.68，p < 0.00001），但在缺乏生物标志物的患者中没有获益（HR 0.94，95% CI 0.82-1.08；p = 0.38）。亚组分析显示BRCA基因状态和SFLN11生物标志物能够预测到获益，并且生物标志物驱动的获益发生在卵巢癌、乳腺癌和小细胞肺癌中。将PARP抑制剂与化疗联合应用与高达3/4级的副作用，尤其是中性粒细胞减少相关联。只有在能够识别出DNA修复生物标志物的患者中，联合治疗才能改善PFS。这表明，PARP抑制剂只有在患者的肿瘤存在同源重组缺陷或其他影响DNA修复的生物标志物时才能增强其对化疗的敏感性。虽然对具有DNA修复生物标志物的患者有效，但联合治疗使用可能会产生高级别的血液系统副作用。因此，在权衡联合治疗的PFS获益时，必须考虑潜在的不良反应，因为单独治疗也可能带来一定的获益。版权所有 © 2023。由Elsevier Ltd. 发布。

The addition of PARP inhibitors to chemotherapy has been assessed in >80 clinical trials across multiple malignancies, on the premise that PARP inhibitors will increase chemotherapy effectiveness regardless of whether cancers have underlying disruption of DNA repair pathways. Consequently, the majority of combination therapy trials have been performed on patients without biomarker selection, despite the use of homologous recombination deficiency to dictate use of PARP inhibitors in the maintenance setting. An unresolved question is whether biomarkers are needed to identify patients who respond to combination PARP inhibitors and chemotherapy.A systematic literature review identified studies using PARP inhibitors in combination with chemotherapy versus chemotherapy alone, where the study included a biomarker of DNA repair function (BRCA1, BRCA2, homologous recombination deficiency test, ATM, ERCC1, SFLN11). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance, and fixed or random effects modelling. Subgroup analyses were conducted on biomarker selection and type of malignancy.Nine studies comprising 2,547 patients met the inclusion criteria. Progression-free survival (PFS) was significantly better in patients with a DNA repair biomarker (HR: 0.57, 95% CI: 0.48-0.68, p < 0.00001), but there was no benefit in patients who lacked a biomarker (HR 0.94, 95% CI 0.82-1.08; p = 0.38). Subgroup analysis showed that BRCA status and SFLN11 biomarkers could predict benefit, and biomarker-driven benefit occurred in ovarian, breast and small cell lung cancers. The addition of PARP inhibitors to chemotherapy was associated with increased grade 3/4 side effects, and particularly neutropenia.Combination therapy only improves PFS in patients with identifiable DNA repair biomarkers. This indicates that PARP inhibitors do not sensitise patients to chemotherapy treatment, except where their cancer has a homologous recombination defect, or an alternative biomarker of altered DNA repair. While effective in patients with DNA repair biomarkers, there is a risk of high-grade haematological side-effects with the use of combination therapy. Thus, the benefit in PFS from combination therapy must be weighed against potential adverse effects, as individual arms of treatment can also confer benefit.Copyright © 2023. Published by Elsevier Ltd.