Multicenter phase 3 trial of fuzuloparib with or without apatinib for HER2-negative metastatic breast cancer with germline BRCA1/2 mutations

Addition of anti-angiogenic inhibitors has the potential to enhance the efficacy of PARP inhibitors. The phase 3 FABULOUS trial, at 40 centers in China, evaluated the fuzuloparib (PARP inhbitor) with or without apatinib (angiogenesis inhibitor) in women with HER2-negative metastatic breast cancer (mBC) with deleterious germline BRCA1/2 mutations and an ECOG performance status of 0 or 1. Patients were randomized 1:1:1 to fuzuloparib plus apatinib (n=70), fuzuloparib monotherapy (n=67), or chemotherapy of physician’s choice (capecitabine or vinorelbine; n=66). The primary endpoint was progression-free survival per blinded independent central review. Interim analysis of the trial has now been published. The median PFS was 11.0 months (95% CI 8.4-13.1) with fuzuloparib plus apatinib, 6.7 months (4.2-7.6) with fuzuloparib, and 3.0 months (1.6-5.3) with chemotherapy. Compared with chemotherapy, fuzuloparib plus apatinib (HR 0.27; p<0.0001) and fuzuloparib monotherapy (HR 0.49; p=0.0004) groups had significantly longer PFS. Additionally, the fuzuloparib plus apatinib had significantly longer PFS than the fuzuloparib monotherapy group (HR 0.60; p=0.0079). Serious treatment-related adverse events occurred in 13%, 18%, and 14% in the three groups, and fatal TRAEs in none, one, and none patients, respectively. The authors conclude that fuzuloparib, either as monotherapy or in combination with apatinib, provided statistically significant improvement in PFS compared with chemotherapy in patients with HER2-negative mBC and germline BRCA1/2 mutations.