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

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.

• Authors: 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
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 197 Issue 3 Pg. 489-501 (Feb 2023) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 36459284 (Publication Type: Multicenter Study, Clinical Trial, Phase II, Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Fluorenes
• pamiparib
• Receptor, ErbB-2
• BRCA2 protein, human
• BRCA1 protein, human

Topics

• Adult
• Aged
• Female
• Humans
• Middle Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Fluorenes (therapeutic use)
• Germ Cells (metabolism)
• Mutation
• Receptor, ErbB-2 (genetics, metabolism)
• Triple Negative Breast Neoplasms (drug therapy, genetics)