To the Editor We have read the recently published studies by Vinayak et al¹ and Konstantinopoulos et al² investigating the regimen of niraparib plus pembrolizumab in patients with triple-negative breast cancer (TNBC) or ovarian cancer with great interest. Results of this preliminary trial, the TOPACIO/KEYNOTE-162 (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer) trial, demonstrate a tolerable safety profile and promising effectiveness of niraparib combined with pembrolizumab for treatment of refractory TNBC¹ or platinum-resistant ovarian cancer.² Although the findings are appealing, we believe that the results of biomarker analysis on the mutation status of BRCA or homologous recombination repair (HRR) must be interpreted with caution. According to the published data,^1,2 the objective response rate (ORR) for patients with platinum-resistant ovarian cancer was not associated with tumor BRCA (tBRCA) mutation or HRR deficiency. In patients with TNBC, intriguingly, those with tBRCA mutation had higher ORR, higher disease control rate, and longer progression-free survival than those without confirmed tBRCA mutation. Herein, we propose 3 aspects that should be highlighted in analyzing the predictive role of BRCA mutations and HRR deficiency and need to be emphasized in future phase 3 clinical investigations.

致编辑我们已经阅读了Vinayak等人¹和Konstantinopoulos等人²最近发表的研究，这些研究对三阴性乳腺癌（TNBC）或卵巢癌患者中的尼拉帕利+派姆单抗的治疗方案产生了浓厚的兴趣。这项初步试验的结果为TOPACIO / KEYNOTE-162（尼拉帕尼与三氯阴性乳腺癌或卵巢癌患者的派姆单抗联合使用）试验，显示了可耐受的安全性和尼拉帕单抗与派姆单抗联合治疗难治性TNBC的有希望的疗效^1例或铂耐药性卵巢癌。²尽管这些发现很吸引人，但我们认为生物标志物分析的结果表明其突变状态必须谨慎解释BRCA或同源重组修复（HRR）。根据公布的数据，^{1 ，2}的客观响应率（ORR）患者的铂类耐药卵巢癌与肿瘤相关的BRCA（吨BRCA）突变或HRR缺乏。在患者三阴，有趣的是，那些与T BRCA基因突变有较高的ORR，较高的疾病控制率，而且比那些没有证实t长的无进展生存BRCA突变。在本文中，我们提出了三个方面，在分析BRCA突变和HRR缺乏的预测作用时应强调三个方面，在未来的3期临床研究中需要强调这些方面。