Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study

Binghe Xu, Tao Sun, Yanxia Shi, Jiuwei Cui, Yongmei Yin, Quchang Ouyang, Qiang Liu, Qingyuan Zhang, Yiding Chen, Shouman Wang, Xiaojia Wang, Zhongsheng Tong, Yahua Zhong, Jiayu Wang, Min Yan, Xi Yan, Chuan Wang, Jifeng Feng, Xiuli Wang, Gang Hu, Ying Cheng, Ruimin Ge, Zhaoyin Zhu, Wa Zhang, Zhimin Shao, Binghe Xu, Tao Sun, Yanxia Shi, Jiuwei Cui, Yongmei Yin, Quchang Ouyang, Qiang Liu, Qingyuan Zhang, Yiding Chen, Shouman Wang, Xiaojia Wang, Zhongsheng Tong, Yahua Zhong, Jiayu Wang, Min Yan, Xi Yan, Chuan Wang, Jifeng Feng, Xiuli Wang, Gang Hu, Ying Cheng, Ruimin Ge, Zhaoyin Zhu, Wa Zhang, Zhimin Shao

Abstract

Purpose: 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).

Methods: 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.

Results: 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.

Conclusion: Pamiparib showed encouraging efficacy and an acceptable safety profile in patients with locally advanced and metastatic HER2- breast cancer with gBRCA1/2 m.

Trial registration: ClinicalTrials.gov, NCT03575065; July 2, 2018.

Keywords: BRCA mutation; Breast cancer; Clinical trial; PARP inhibitor; Pamiparib.

Conflict of interest statement

Binghe Xu reports receiving advisory fees from Novartis and Roche, and fees for serving on a speakers’ bureau from AstraZeneca, Pfizer, Roche, and Eisai. Tao Sun, Yanxia Shi, Jiuwei Cui, Yongmei Yin, Quchang Ouyang, Qiang Liu, Qingyuan Zhang, Yiding Chen, Shouman Wang, Xiaojia Wang, Zhongsheng Tong, Yahua Zhong, Jiayu Wang, Min Yan, Xi Yan, Chuan Wang, Jifeng Feng, Xiuli Wang, Gang Hu, Ying Cheng, and Zhimin Shao have no relevant financial or non-financial interests to disclose. Ruimin Ge, Zhaoyin Zhu, and Wa Zhang are employees of BeiGene, Ltd., and have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Subgroup analysis: ORR by IRC in the TNBC cohort in the efficacy analysis set. The two-sided 95% CI was calculated using the binomial exact method. The historical ORR with chemotherapy in a similar population is represented by a dashed line on the figure and was estimated to be 25%. Data cutoff: October 9, 2020. BRCA breast cancer susceptibility gene, CI confidence interval, ECOG Eastern Cooperative Oncology Group, IRC independent review committee, ORR objective response rate, TNBC triple-negative breast cancer
Fig. 2
Fig. 2
Best percentage change in target lesion diameter by IRC in patients in the a TNBC cohort and b HR+/HER2− cohort, grouped by prior lines of chemotherapy in the efficacy analysis set. HER2- human epidermal growth factor receptor 2-negative, HR + hormone receptor-positive, IRC independent review committee, TNBC triple-negative breast cancer
Fig. 3
Fig. 3
PFS by IRC in the a TNBC cohort and b HR+/HER2− cohort, and OS in the c TNBC cohort and d HR+/HER2− cohort in the safety analysis set. Median PFS and OS were estimated by the Kaplan–Meier method, with 95% CIs estimated using the method of Brookmeyer and Crowley. CI confidence interval, HER2− human epidermal growth factor receptor 2-negative, HR+ hormone receptor-positive, IRC independent review committee, NE not estimable, OS overall survival, PFS progression-free survival, TNBC triple-negative breast cancer

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Source: PubMed

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