Fuzuloparib ± Apatinib Improves PFS in BRCA+ Metastatic Breast Cancer

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Phase 2 data support the use of fuzuloparib with or without apatinib in HER2-negative metastatic breast cancer harboring BRCA1/2 germline mutations.

"Taken together, our findings support the use of fuzuloparib plus apatinib or fuzuloparib alone in [patients with] HER2-negative metastatic breast cancer with a germline BRCA mutation," according to study author Huiping Li.

"Taken together, our findings support the use of fuzuloparib plus apatinib or fuzuloparib alone in [patients with] HER2-negative metastatic breast cancer with a germline BRCA mutation," according to study author Huiping Li.

Treatment with fuzuloparib alone or in combination with apatinib (Rivoceranib) improved progression-free survival (PFS) compared with chemotherapy in patients with HER2-negative metastatic breast cancer harboring germline BRCA mutations, according to findings from a phase 3 trial (NCT04296370) presented during a European Society for Medical Oncology (ESMO) Virtual Plenary Session.

Based on blinded independent central review (BICR), the median PFS was 11.0 months (95% CI, 8.4-13.1) with fuzuloparib/apatinib, 6.7 months (95% CI, 4.2-7.6) with fuzuloparib monotherapy, and 3.0 months (95% CI, 1.6-5.3) with chemotherapy. Compared with chemotherapy, significant PFS improvements were reported in the fuzuloparib/apatinib (HR, 0.27; 95% CI, 0.17-0.43; P <.0001) and fuzuloparib alone arms (HR, 0.49; 95% CI, 0.32-0.75; P = .0004). Additionally, fuzuloparib and apatinib combination therapy conferred an improvement in PFS compared with fuzuloparib alone (HR, 0.60; 95% CI, 0.40-0.91; P = .0079).

“The profile and severity of toxicity were consistent with previous reports of fuzuloparib and apatinib,” study author Huiping Li, from the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) in the Department of Breast Oncology at Peking University Cancer Hospital and Institute, Beijing, China, said in the presentation. “Taken together, our findings support the use of fuzuloparib plus apatinib or fuzuloparib alone in [patients with] HER2-negative metastatic breast cancer with a germline BRCA mutation.”

In this open-label, multicenter phase 3 study, 203 patients were randomly assigned to receive fuzuloparib at 100 mg orally twice a day plus apatinib orally at 500 mg once a day (n = 70), fuzuloparib alone at 150 mg orally twice a day (n = 67), or physician’s choice of chemotherapy (n = 66). Treatment in the chemotherapy arm consisted of capecitabine or vinorelbine administered as part of a continuous 21-day schedule.

The trial’s primary end point was PFS by BICR. Secondary end points included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety.

Patients 18 to 75 years old with pathologically confirmed HER2-negative breast cancer and a confirmed or suspected deleterious germline BRCA1/2 mutation were eligible for enrollment on the trial. Additional eligibility criteria included having prior treatment with an anthracycline and/or a taxane, a maximum of 2 prior lines of chemotherapy for recurrent or metastatic disease, 1 or more lines of endocrine therapy for hormone receptor–positive disease, and an ECOG performance status of 0 or 1.

The median age was 49.0 years (range, 39.0-55.0) in the fuzuloparib/apatinib arm, 49.0 years (range, 39.0-56.0) in the fuzuloparib arm, and 47.5 years (range, 40.0-55.0) in the chemotherapy arm. Across each respective arm, most patients had germline BRCA2 mutations (62.9% vs 61.2% vs 53.0%), hormone receptor–positive disease (58.6% vs 62.1% vs 62.1%), 1 or more prior lines of chemotherapy (70.0% vs 74.6% vs 72.7%), and measurable disease at baseline (74.3% vs 82.1% vs 65.2%).

The median OS was 29.2 months (95% CI, 24.6-not reached [NR]) with the combination regimen, 31.5 months (95% CI, 17.8-NR) with fuzuloparib monotherapy, and 21.5 months (95% CI, 15.6-31.9) with chemotherapy. Compared with chemotherapy, data highlighted an OS benefit with fuzuloparib/apatinib (HR, 0.58; 95% CI, 0.33-1.02) and fuzuloparib alone (HR, 0.61; 95% CI, 0.35-1.08), even with 39.4% of patients in the chemotherapy arm crossing over to fuzuloparib monotherapy.

The ORR was 67.3% (95% CI, 52.9%-79.7%) with combination therapy, 43.6% (95% CI, 30.3%-57.7%) with fuzuloparib alone, and 23.3% (95% CI, 11.8%-38.6%) in the chemotherapy arm. In each respective arm, the DCR was 87.1% (95% CI, 77.0%-93.9%), 80.6% (95% CI, 69.1%-89.2%), and 47.0% (95% CI, 34.6%-59.7%). Additionally, the median DOR was 9.8 months (95% CI, 7.0-11.8), 7.6 months (95% CI, 5.5-14.0), and 3.9 months (95% CI, 2.6-12.5), respectively.

Any-grade treatment-related adverse effects affected 98.6%, 92.5%, and 93.2% of patients in the fuzuloparib/apatinib, fuzuloparib monotherapy, and chemotherapy arms, respectively. In each respective, the rates of grade 3 TRAEs were 51.4%, 49.3%, and 40.7%; serious TRAEs occurred in 12.9%, 17.9%, and 13.6%. One patient in the fuzuloparib monotherapy arm experienced a TRAE leading to death.

In the combination therapy, monotherapy, and chemotherapy arms, respectively, common any-grade TRAEs included white blood cell count decreases (64.3% vs 59.7% vs 54.2%), neutrophil count decreases (51.4% vs 53.7% vs 54.2%), and nausea (45.7%). Grade 3 or higher TRAEs in each arm included neutrophil count decreases (12.9% vs 20.9% vs 23.7%), anemia (11.4% vs 37.3% vs 8.5%), and platelet count decreases (10.0% vs 11.9% vs 0.0%).

Reference

Li H, Liu J, Liu Y, et al. Fuzuloparib with or without apatinib in HER2- metastatic breast cancer (mBC) patients (pts) with germline BRCA1/2 mutations (gBRCA1/2m): a randomized phase III trial. Presented at the 2024 European Society for Medical Society Virtual Plenary Session; May 9, 2024.

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