In an interim analysis of a Chinese phase III trial (FZOCUS-2) reported in the Journal of Clinical Oncology, Li et al found that maintenance treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor fuzuloparib significantly prolonged progression-free survival vs placebo in patients with high-grade ovarian cancer responding to second- or later-line platinum-based chemotherapy, including in patients with germline BRCA1/2 mutations.

Study Details

In the multicenter double-blind trial, 252 patients were randomly assigned 2:1 between April 2019 and January 2020 to receive fuzuloparib at 150 mg twice daily (n = 167) or placebo (n = 85) in 28-day cycles. The primary endpoints were progression-free survival assessed by blinded independent review committee in the overall population and in the subpopulation with germline BRCA1/2 mutations.

Key Findings

The median duration of follow-up was 8.5 months (range = 0.1–14.1 months).

Median progression-free survival was 12.9 months (95% confidence interval [CI] = 11.1 months–not reached) in the fuzuloparib group vs 5.5 months (95% CI = 3.8–5.6 months) in the placebo group (hazard ratio [HR] = 0.25, 95% CI = 0.17–0.36, P < .0001).

Progression-free survival was significantly prolonged with fuzuloparib among both 66 vs 34 patients with germline BRCA1/2 mutations (HR = 0.14, 95% CI = 0.07–0.28) and among 101 vs 51 without such mutations (HR = 0.46, 95% CI = 0.29–0.74).

Grade 3 or 4 adverse events occurred in 47.9% of patients in the fuzuloparib group vs 10.7% in the placebo group. The most common in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). One patient in fuzuloparib group discontinued treatment due to a treatment-related adverse event, and one patient in the fuzuloparib group died from an adverse event (sudden cardiac death) considered unrelated to treatment.

The investigators concluded, “Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in progression-free survival for patients with platinum-sensitive, recurrent ovarian cancer vs placebo, regardless of germline BRCA 1/2 mutation [status], and showed a manageable safety profile.”

Lingying Wu, MD, PhD, of the Chinese Academy of Medical Sciences and Peking Union Medical College Cancer Hospital Chinese Academy of Medical Sciences, Beijing, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Jiangsu Hengrui Pharmaceuticals Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.