National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Breast Medicine, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, China.
Breast Cancer Res Treat. 2023 Feb;197(3):489-501. doi: 10.1007/s10549-022-06785-z. Epub 2022 Dec 2.
To evaluate the efficacy and safety of pamiparib in patients with locally advanced or metastatic human epidermal growth factor receptor 2-negative (HER2-) breast cancer, with deleterious or suspected deleterious germline BRCA1/2 mutations (gBRCA1/2 m).
In this open-label, phase II, multicenter study in China (NCT03575065), patients with triple-negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2- breast cancer (HR+/HER2- cohort) and ≤ 2 prior lines of chemotherapy received pamiparib 60 mg orally twice daily in 28-day, continuous cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee.
In total, 88 patients were enrolled (TNBC cohort: 62; HR+/HER2- cohort: 26). Median age was 45.5 (range: 27-67) years, and 60 patients (68.2%) had received 1 or 2 prior lines of chemotherapy; 42 patients (47.7%) had previously received platinum chemotherapy. In the TNBC cohort, ORR was 38.2% (95% confidence interval [CI] 25.4-52.3) and median duration of response (DoR) was 7.0 months (95% CI 3.9-not estimable). In the HR+/HER2- cohort, ORR was 61.9% (95% CI 38.4-81.9) and median DoR was 7.5 months (95% CI 5.6-14.8). The most common treatment-emergent adverse events (TEAEs), treatment-related TEAEs, and ≥ Grade 3 TEAEs were hematologic (including anemia, decreased neutrophil count, and decreased white blood cell count). Overall, 64.8% of patients had TEAEs leading to dose reduction and 2.3% had TEAEs leading to treatment discontinuation.
Pamiparib showed encouraging efficacy and an acceptable safety profile in patients with locally advanced and metastatic HER2- breast cancer with gBRCA1/2 m.
ClinicalTrials.gov, NCT03575065; July 2, 2018.
评估帕米帕利在局部晚期或转移性人表皮生长因子受体 2 阴性（HER2-）乳腺癌、种系 BRCA1/2 突变（gBRCA1/2m）有害或疑似有害的患者中的疗效和安全性。
在中国开展的这项开放标签、II 期、多中心研究（NCT03575065）中，三阴性乳腺癌（TNBC 队列）或激素受体阳性（HR+）/HER2-乳腺癌（HR+/HER2- 队列）患者且既往接受过≤2 线化疗，接受帕米帕利 60mg 口服、每日 2 次，每 28 天为一个周期。主要终点为独立评审委员会评估的客观缓解率（ORR；RECIST v1.1）。
共纳入 88 例患者（TNBC 队列 62 例，HR+/HER2- 队列 26 例）。中位年龄为 45.5 岁（范围：27-67 岁），60 例患者（68.2%）接受过 1 线或 2 线化疗；42 例患者（47.7%）曾接受过铂类化疗。在 TNBC 队列中，ORR 为 38.2%（95%CI 25.4-52.3），中位缓解持续时间（DoR）为 7.0 个月（95%CI 3.9-无法评估）。在 HR+/HER2-队列中，ORR 为 61.9%（95%CI 38.4-81.9），中位 DoR 为 7.5 个月（95%CI 5.6-14.8）。最常见的治疗相关不良事件（TRAEs）、治疗相关 TRAEs 和≥3 级 TRAEs 为血液学毒性（包括贫血、中性粒细胞计数降低和白细胞计数降低）。总体而言，64.8%的患者因 TRAEs 而减少剂量，2.3%的患者因 TRAEs 而停止治疗。
帕米帕利在局部晚期和转移性 HER2-乳腺癌、种系 BRCA1/2m 患者中显示出令人鼓舞的疗效和可接受的安全性。
ClinicalTrials.gov，NCT03575065；2018 年 7 月 2 日。
