Fuzuloparib as maintenance therapy prolongs survival in advanced ovarian cancer

Maintenance therapy with fuzuloparib results in significant improvements in progression-free survival (PFS) in patients newly diagnosed with advanced ovarian cancer, who showed response to first-line platinum-based chemotherapy (PBC), reports a study (FZOCUS-1) presented at SGO 2024.

In addition, fuzuloparib displays a manageable safety profile, with no treatment-related adverse event (TRAE) leading to death.

“Our data support fuzuloparib as a new treatment option in this setting,” said lead investigator Dr Lingying Wu from the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

“The trial is ongoing to further assess the therapeutic effects of adding apatinib to fuzuloparib maintenance,” Wu added.

FZOCUS-1, a randomized, placebo-controlled, phase III trial, enrolled 674 patients with a newly diagnosed FIGO stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer, who had cytoreductive surgery and achieved complete (CR) or partial response (PR) following first-line PBC.

Participants (germline [g]BRCA1/2 mutation, 31.4 percent; interval cytoreductive surgery, 41.7 percent; R2 resection, 44.4 percent) were randomly assigned (2:2:1) to orally receive fuzuloparib (150 mg BID; n=269), fuzuloparib (100 mg BID) plus apatinib (a VEGFR-2 inhibitor; 375 mg QD; n=269), or matching placebo (n=136) as maintenance therapy.

PFS per RECIST v1.1 served as the primary endpoint, with testing fuzuloparib versus placebo in the overall population and gBRCA1/2-mutated subpopulation as the main objectives.

Longer PFS

Wu and colleagues conducted a prespecified interim analysis, with a median follow-up of 21.0 months in the fuzuloparib group and 20.8 months in the placebo group. A total of 297 PFS events (66.6 percent of total expected) occurred as of 31 March 2023. [Wu, L, et al, SGO 2024]

In the overall population, patients who received fuzuloparib achieved significantly longer BIRC-assessed PFS compared with those on placebo (median, not reached [NR] vs 11.1 months; hazard ratio [HR], 0.49, 95 percent confidence interval [CI], 0.37‒0.67; 1-sided p<0.0001).

In patients with gBRCA1/2 mutation, median PFS was NR with fuzuloparib compared with 14.9 months with placebo (HR, 0.40, 95 percent CI, 0.22‒0.73; 1-sided p<0.0001).  Median PFS in those without gBRCA1/2 mutation was 25.5 months with fuzuloparib versus 8.4 months with placebo (HR, 0.53, 95 percent CI, 0.37‒0.75).

Notably, “[t]he PFS benefits with fuzuloparib were generally consistent across clinically relevant subgroups,” said Wu.

In addition, median overall survival in both groups was NR, with a trend favouring fuzuloparib (HR, 0.54, 95 percent CI, 0.28‒1.03).

“Fuzuloparib as maintenance therapy significantly improved PFS in patients with newly diagnosed advanced ovarian cancer, following a response to first-line PBC,” Wu said.

Manageable safety

In terms of safety, grade 3 and above TRAEs occurred in 44.6 percent of patients treated with fuzuloparib. The most common TRAE was anaemia (23.4 percent), followed by decreased platelet count (12.3 percent) and decreased neutrophil count (10.8 percent).

Very few patients (0.7 percent) discontinued treatment with fuzuloparib due to TRAE. Moreover, no myelodysplastic syndrome, acute myeloid leukaemia, or treatment-related deaths occurred.

“Fuzuloparib is a novel PARP inhibitor with established efficacy as a treatment for platinum-sensitive, gBRCA1/2-mutated recurrent ovarian cancer and as maintenance therapy for platinum-sensitive, recurrent ovarian cancer progressing after [two or more] lines of PBC,” Wu said.