Fuzuloparib Enhances PFS in Newly Diagnosed Advanced OC

Fuzuloparib (fluzoparib) is a novel PARP inhibitor utilized in platinum-sensitive, germline BRCA1/2 (gBRCA1/2)-mutated recurrent ovarian cancer (OC) treatment and as maintenance therapy in recurrent OC following ≥2 lines of platinum-based chemotherapy (PBC).

In this double-blind, randomized phase 3 trial, Lingying Wu and the team aimed to further explore fuzuloparib’s efficacy and safety, both as monotherapy and in combination with apatinib (a VEGFR-2 inhibitor) in the first-line maintenance setting for advanced OC.

Researchers performed an inclusive analysis on patients with newly diagnosed FIGO stage III/IV epithelial ovarian, fallopian-tube, or primary peritoneal cancer who underwent cytoreductive surgery and achieved complete or partial response after first-line platinum-based chemotherapy. These patients were enrolled and randomized (2:2:1) to receive orally administered fuzuloparib (150 mg BID), fuzuloparib (100 mg BID) + apatinib (375 mg QD), or matching placebo as maintenance therapy.

The primary endpoint, progression-free survival (PFS) per RECIST v1.1 assessed by BIRC, was evaluated with fuzuloparib compared to placebo in both the overall population and the germline BRCA1/2-mutated sub-population. As of March 31, 2023, 297 PFS events (66.6% of total expected) had occurred, prompting a prespecified interim analysis. Results comparing fuzuloparib versus placebo in the interim analysis are reported herein.

About 674 patients were randomly assigned and treated, including 269 receiving fuzuloparib and 136 receiving placebo, with 31.4% having gBRCA1/2 mutation, 41.7% undergoing interval cytoreductive surgery, and 44.4% achieving R2 resection. Median follow-up was 21.0 months in the fuzuloparib group and 20.8 months in the placebo group.

BIRC-assessed PFS was significantly prolonged with fuzuloparib versus placebo in the overall population (median not reached [NR] vs 11.1 months; HR 0.49, 95% CI 0.37-0.67; 1-sided P <0.0001). Median PFS by BIRC was NR with fuzuloparib versus 14.9 months with placebo in patients with gBRCA1/2 mutation (HR 0.40, 95% CI 0.22-0.73; 1-sided P <0.0001), and 25.5 months versus 8.4 months in patients without gBRCA1/2 mutation (HR 0.53, 95% CI 0.37-0.75). PFS benefits with fuzuloparib were consistent across clinically relevant subgroups.

Median overall survival (OS) was NR in both groups, with a trend favoring fuzuloparib (HR 0.54, 95% CI 0.28-1.03). Grade ≥3 treatment-related adverse events (TRAEs) were reported in 44.6% of patients in the fuzuloparib group, with the most common being anemia (23.4%), decreased platelet count (12.3%), and decreased neutrophil count (10.8%). Fuzuloparib discontinuation due to TRAE occurred in 0.7% of patients. No cases of myelodysplastic syndrome, acute myeloid leukemia, or treatment-related deaths were observed.

The study concluded that fuzuloparib as maintenance therapy significantly improves PFS with a manageable safety profile in patients with newly diagnosed advanced ovarian cancer following a response to first-line platinum-based chemotherapy.

These findings supported fuzuloparib as a new treatment option in this setting. The ongoing trial aims to further assess the therapeutic effects of adding apatinib to fuzuloparib maintenance.

The trial was sponsored by Jiangsu HengRui Medicine Co., Ltd.

Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=440521&CONF=AM2024&CKEY=

Clinical Trial: https://clinicaltrials.gov/study/NCT04229615

Wu L, Li N, Wang J, et al. (2024). “Fuzuloparib as maintenance therapy among patients with advanced ovarian cancer after a response to first-line platinum-based chemotherapy: Results from a randomized, placebo-controlled, phase III trial.” Presented at SGO 2024.