In an interim analysis of a Chinese phase III trial (FABULOUS) reported in The Lancet Oncology, Li et al found that the addition of the PARP inhibitor fuzuloparib to apatinib and fuzuloparib alone improved progression-free survival vs chemotherapy in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations.
Study Details
In the multicenter open-label trial, 203 eligible patients were randomly assigned 1:1:1 between October 2020 and December 2023 to receive fuzuloparib at 100 mg twice daily plus oral apatinib at 500 mg once daily (n = 70), fuzuloparib at 150 mg twice daily (n = 67), or physician choice of chemotherapy (n = 66; capecitabine at 1,000–1,250 mg/m² twice daily on days 1–14 or vinorelbine at 25–30 mg/m² on days 1 and 8 of each 21-day cycle). Treatment continued until progression (unless investigators deemed there to be continued benefit in patients receiving fuzuloparib) or unacceptable toxicity. The primary endpoint was progression-free survival on blinded independent central review assessment.
Key Findings
At interim analysis, median time from random assignment to cutoff date was 24.2 months (interquartile range = 13.2–31.8 months).
Median progression-free survival was 11.0 months (95% confidence interval [CI] = 8.4–13.1 months) in the fuzuloparib plus apatinib group (hazard ratio [HR] vs chemotherapy = 0.27, 95% CI = 0.17–0.43, P < .0001), 6.7 months (95% CI = 4.2–7.6 months) in the fuzuloparib group (HR vs chemotherapy = 0.49, 95% CI = 0.32–0.75, P = .0004), and 3.0 months (95% CI = 1.6–5.3 months) in the chemotherapy group. In addition, the fuzuloparib plus apatinib group had significantly prolonged progression-free survival vs the fuzuloparib group (HR = 0.60, 95% CI = 0.40–0.91, P = .0079).
Grade 3 or worse treatment-related adverse events occurred in 51% of the fuzuloparib plus apatinib group (most commonly decreased neutrophils [13%], hypertension [13%], and anemia [11%]); 49% of the fuzuloparib group (most commonly anemia [37%], decreased neutrophils [21%], and decreased white blood cells [19%]); and 41% of the chemotherapy group (most commonly decreased neutrophils [24%] and decreased white blood cells [19%]). Serious treatment-related adverse events occurred in 13%, 18%, and 14% of patients. One treatment-related death was observed in the fuzuloparib monotherapy group (from sepsis).
The investigators concluded: “Fuzuloparib, either as monotherapy or in combination with apatinib, provided statistically significant improvements in progression-free survival compared with chemotherapy in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations, presenting as new treatment options.”
Erwei Song, MD, of Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Jiangsu Hengrui Pharmaceuticals, Natural Science Foundation of China, National Key Research and Development Program of China, and others. For full disclosures of all study authors, visit thelancet.com.
