On December 3, 2024, Hengrui Pharmaceutical Co., Ltd. received the Drug Registration Certificates forFuzuloparib Capsules and Apatinib Mesylate Tablets approved and issued by the National Medical Products Administration (NMPA). The NMPA approved the addition of new indications:Fuzuloparib monotherapy orFuzuloparib in combination with apatinib mesylate for adult patients with germline BRCA mutation (gBRCAm)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have received prior chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. For patients with hormone receptor (HR)-positive breast cancer, prior endocrine therapy or ineligibility for endocrine therapy is required. This indication was previously granted priority review by the Center for Drug Evaluation (CDE) of the NMPA.
Basis for the Approval of These Indications
The approval of these new indications is based on a Phase III clinical trial (the FABULOUS study) ofFuzuloparib monotherapy orFuzuloparib combined with apatinib in patients with gBRCAm-positive, HER2-negative breast cancer. The results demonstrated that bothFuzuloparib plus apatinib andFuzuloparib monotherapy significantly improved progression-free survival (PFS) assessed by blinded independent central review (BICR) compared with standard chemotherapy, and also showed a favorable trend toward overall survival (OS) benefit.
This marks the 4th and 5th approved indications forFuzuloparib (monotherapy and combination therapy, respectively) and the 4th approved indication for apatinib. These approvals will provide new therapeutic options for patients with HER2-negative metastatic breast cancer.
Urgent Unmet Medical Need for the Treatment of BRCA-Mutated Breast Cancer
According to data released by the International Agency for Research on Cancer (IARC) of the World Health Organization in 2020, breast cancer has become the most commonly diagnosed cancer worldwide and one of the most prevalent malignancies in women. In China, the incidence of breast cancer has risen rapidly and now ranks first among all cancers in women, with nearly 50% of patients experiencing recurrence and metastasis after treatment.
Breast cancer susceptibility genes (BRCA), including BRCA1 and BRCA2, are crucial tumor suppressor genes in humans. Compared with the general population, carriers of BRCA1 and BRCA2 mutations have a 10–20-fold higher risk of developing breast cancer. Approximately 5%–10% of breast cancer patients harbor BRCA gene mutations, and BRCA-mutated breast cancer is often associated with advanced stage and poor prognosis. In China, platinum-based chemotherapy remains the mainstay of treatment for BRCA-mutated breast cancer, with a lack of effective targeted therapeutic options.
The FABULOUS Study Brings New Clinical Benefits to Breast Cancer Treatment
The approval of these indications is supported by the Phase III FABULOUS trial, which evaluatedFuzuloparib monotherapy orFuzuloparib combined with apatinib in patients with gBRCAm-positive, HER2-negative breast cancer. The study was led by Principal Investigators Professor Song Erwei from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, and Professor Li Huiping from Peking University Cancer Hospital, with participation from 59 clinical centers across China.
Study Endpoints
Primary endpoint: PFS assessed by BICR
Secondary endpoints: investigator-assessed PFS, time to second progression or death (PFS-2), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), OS, and safety
The primary objectives were to evaluate the potential superiority ofFuzuloparib plus apatinib andFuzuloparib monotherapy over chemotherapy in terms of BICR-assessed PFS, as well as the superiority of combination therapy over monotherapy.
Study Design
Eligible patients were randomized 1:1:1 to receive one of the following regimens:
Fluzoparib (100 mg twice daily [bid]) combined with apatinib (500 mg once daily [qd])
Fluzoparib monotherapy (150 mg bid)
Standard chemotherapy
In the chemotherapy arm, patients were permitted to cross over toFuzuloparib monotherapy after disease progression (PD) was confirmed by BICR.
As of the data cutoff for the current analysis, the study had met its primary endpoint and key secondary endpoints.
