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Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a
Binghe Xu1, Tao Sun2, Yanxia Shi3
1National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. xubinghe@csco.org.cn.
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.
Insights
Pamiparib demonstrated promising efficacy in treating advanced HER2- breast cancer with BRCA mutations. The study found acceptable safety, with manageable side effects in patients with germline BRCA1/2 mutations.
Area of Science:
- Oncology
- Medical Genetics
- Clinical Pharmacology
Background:
- PARP inhibitors represent a targeted therapy approach for cancers with DNA repair deficiencies.
- Germline BRCA1/2 mutations are associated with increased susceptibility to DNA damaging agents.
- Identifying effective treatments for HER2- breast cancer with gBRCA1/2 mutations is crucial.
Purpose of the Study:
- To assess the efficacy and safety of pamiparib in patients with locally advanced or metastatic HER2- breast cancer.
- To evaluate pamiparib in patients harboring deleterious or suspected deleterious germline BRCA1/2 mutations (gBRCA1/2 m).
Main Methods:
- An open-label, phase II, multicenter study (NCT03575065) was conducted in China.
- Patients with triple-negative breast cancer (TNBC) or hormone receptor-positive (HR+)/HER2- breast cancer received pamiparib 60 mg orally twice daily.
- The primary endpoint was objective response rate (ORR) by independent review committee.
Main Results:
- 88 patients were enrolled; 62 in the TNBC cohort and 26 in the HR+/HER2- cohort.
- ORR was 38.2% in the TNBC cohort (median DoR 7.0 months) and 61.9% in the HR+/HER2- cohort (median DoR 7.5 months).
- Most common adverse events were hematologic; 64.8% of patients required dose reduction due to TEAEs.
Conclusions:
- Pamiparib demonstrated encouraging efficacy in patients with locally advanced and metastatic HER2- breast cancer with gBRCA1/2 m.
- The drug exhibited an acceptable safety profile, with manageable adverse events.
- Pamiparib represents a potential therapeutic option for this specific breast cancer subgroup.
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