Fuzuloparib maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer: a multicenter, randomized, double-blind, placebo-controlled, phase III trial

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<h3>Objectives:</h3> Fuzuloparib (formerly fluzoparib), a poly (ADP-ribose) polymerase inhibitor, has shown promising antitumor activity and acceptable safety for the treatment of relapsed ovarian cancer patients harboring the <i>BRCA1/2</i> mutation after 2-4 lines of platinum-based chemotherapy in previous phase 2 trial. This study aimed to assess the efficacy and safety of fuzuloparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. <h3>Methods:</h3> This is a multicenter, double-blind, randomized, placebo-controlled, phase 3 trial conducted at 36 sites in China. Eligible patients had platinum-sensitive, relapsed, high-grade serious ovarian, fallopian tube, primary peritoneal or endometrioid ovarian carcinoma (≥grade 2), had received at least two prior platinum-based regimens and had achieved complete or partial response to their last platinum-based regimen. Patients were randomly assigned in a 2:1 ratio to fuzuloparib (150 mg, twice daily) or matching placebo using an interactive web response system. Randomization was stratified by <i>BRCA1/2</i> mutation (presence or absence), progression-free interval after penultimate platinum-based regimen (6-12 months or >12 months) and best response to most recent regimen (complete or partial response). The co-primary endpoints were progression-free survival (PFS) assessed by blinded independent central review (BICR) in the overall population and in the <i>BRCA1/2</i> mutation population. Here, we reported the results of the prespecified interim analysis from this ongoing study, which was planned for formal statistical testing on PFS per BICR in the overall population. <h3>Results:</h3> Between Apr. 30, 2019 and Jan. 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n=167) or placebo (n=85). <i>BRCA1/2</i> mutations were confirmed in 100 (39.7%) patients. Sixty-one (24.2%) patients had received more than two lines of previous platinum-based regimen, and 127 (50.4%) patients had the complete response to the most recent regimen. As of Jul 1, 2020, the median PFS per BICR assessment in the overall population was significantly improved with fuzuloparib (hazard ratio [HR], 0.25; 95% CI, 0.17-0.36; one-sided P<0.0001; Figure 1). The HR derived from prespecified subgroup analyses showed a consistent trend of benefit in patients with <i>BRCA1/2</i> mutation (HR, 0.14, 95% CI, 0.07-0.28) or without it (HR, 0.46; 95% CI, 0.29-0.74). The most common Grade ≥3 adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), decreased neutrophil count (12.6%) and decreased white blood cell count (10.8%), which were manageable with treatment interruption or dose modifications, with only one (0.6%) patient discontinuing treatment due to neutropenia. <h3>Conclusions:</h3> Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, relapsed ovarian cancer compared with placebo, regardless of <i>BRCA1/2</i> mutation, and had a manageable safety profile.