Background:Niraparib is an oral poly (adenosine diphosphate-ribose) polymerase inhibitor with promising activity for patients with advanced breast cancer harboring germlineBRCA1/2 mutations.Methods:LUZERN (NCT04240106) was a multicenter, open-label, Simon’s two-stage, phase II clinical trial evaluating the efficacy and safety of niraparib with aromatase inhibitors (AIs) for patients with HR-positive/HER2-negative advanced breast cancer with either a germlineBRCA1/2 mutation (cohort A) or germlineBRCA1/2 wild-type and homologous recombination deficiency (exploratory cohort B). Eligible patients received ≤1 line of chemotherapy and 1–2 prior lines of endocrine therapy for advanced disease with secondary resistance to the last AI-based regimen. Patients received niraparib (300 mg or 200 mg) plus an AI. The primary endpoint was the clinical benefit rate (CBR) in cohort A.Results:Between June 2020 and November 2022, 14 patients were enrolled in cohort A (n = 6 for stage I, n = 8 for stage II) and no patients were enrolled in cohort B. One patient was excluded from the efficacy analysis due to no prior AI treatment. Nearly all patients (92.9%) previously received a cyclin-dependent kinase 4/6 inhibitor, but no patients had received prior platinum-based chemotherapy. Median follow-up was 16.7 months (range: 13.2–18.2). The CBR was 46.2% (95% CI: 19.2–74.9), meeting the primary endpoint. Median progression-free survival was 5.5 months (95% CI: 1.9–8.5), and median overall survival was 18.1 months (95% CI: 9.7–NE). The safety profile was consistent with the known toxicity of both drugs.Conclusions:Niraparib combined with an AI has encouraging antitumor activity and a manageable safety profile in patients with AI-resistant HR-positive/HER2-negative advanced breast cancer with germlineBRCA1/2 mutations.
背景：尼拉帕利是一种口服聚腺苷二磷酸核糖聚合酶抑制剂，对携带种系BRCA1/2突变的晚期乳腺癌患者显示出良好疗效。方法：LUZERN研究（NCT04240106）是一项多中心、开放标签、西蒙两阶段设计的II期临床试验，旨在评估尼拉帕利联合芳香化酶抑制剂在HR阳性/HER2阴性晚期乳腺癌患者中的疗效与安全性。研究设置两个队列：携带种系BRCA1/2突变队列（队列A）及种系BRCA1/2野生型伴同源重组缺陷探索性队列（队列B）。入组患者需满足：晚期阶段接受过≤1线化疗及1-2线内分泌治疗，且对末次AI方案产生继发耐药。所有患者接受尼拉帕利（300mg或200mg）联合AI治疗。主要终点为队列A的临床获益率。结果：2020年6月至2022年11月期间，队列A共入组14例患者（第一阶段6例，第二阶段8例），队列B未纳入患者。1例患者因未接受过AI治疗被排除出疗效分析。几乎所有患者（92.9%）既往接受过CDK4/6抑制剂治疗，但均未接受过铂类化疗。中位随访时间为16.7个月（范围：13.2-18.2）。临床获益率达46.2%（95% CI：19.2-74.9），达到主要终点。中位无进展生存期为5.5个月（95% CI：1.9-8.5），中位总生存期为18.1个月（95% CI：9.7-未达到）。安全性特征与两种药物的已知毒性相符。结论：对于AI耐药的HR阳性/HER2阴性晚期乳腺癌伴种系BRCA1/2突变患者，尼拉帕利联合AI方案展现出具有前景的抗肿瘤活性及可控的安全性特征。
肿瘤(癌症)患者之家