Fuzuloparib Maintenance Therapies Improve PFS in Newly Diagnosed Ovarian Cancer

Results from the multicenter, randomized phase 3 FZFOCUS-1 trial (NCT04229615) showed that fuzuloparib (AiRuiYi) monotherapy and fuzuloparib plus apatinib (Aitan) combination therapy improved progression-free survival (PFS) compared with placebo in the first-line maintenance of patients with advanced ovarian cancer. These results were shared in CA: A Cancer Journal for Clinicians.

As of the November 1, 2024, data cutoff date, blinded independent review committee (BIRC)-assessed PFS events occurred in 55.8% of the combination therapy group, 53.3% of the fuzuloparib monotherapy group, and 66.9% of the placebo group. Respectively, the median PFS was 26.9 months (95% CI, 20.3-36.6), 29.9 months (95% CI, 22.1-36.1), and 11.1 months (95% CI, 8.3-16.6). The HR for combination therapy vs placebo was 0.57 (95% CI, 0.44-0.75; P <.0001); the HR for fuzuloparib monotherapy vs placebo was 0.58 (95% CI, 0.44-0.75; P <.0001).

In patients harboring germline BRCA1/2 mutations, the HR for combination therapy vs placebo was 0.50 (95% CI, 0.30-0.84; P = .0039). For fuzuloparib monotherapy vs placebo, the HR was 0.51 (95% CI, 0.30-0.86; P = .0050). In patients with germline BRCA1/2 wild-type, the HR was 0.61 (95% CI, 0.45-0.83; P = .0009) for combination therapy vs placebo, the HR was 0.60 (95% CI, 0.44-0.82; P = .0006) for fuzuloparib monotherapy. Across clinically relevant subgroups, the PFS benefits vs placebo remained consistent.

Notably, the combination therapy did not yield additional PFS benefits in either the overall population (HR, 1.04; 95% CI, 0.83-1.32; P = .6393) or the germline BRCA1/2-mutated subpopulation (HR, 1.11; 95% CI, 0.69-1.79; P = .6667).

Among patients harboring homologous recombination-deficient (HRD) disease, the median PFS was 34.1 months (95% CI, 22.4-41.2) in the combination therapy group and 35.8 months (95% CI, 27.3-not reached) in the monotherapy group (HR, 1.09; 95% CI, 0.83-1.44). Among those with homologous recombination-proficient disease, the median PFS was 16.6 months (95% CI, 10.2-22.1) and 11.0 months (95% CI, 6.5-16.6), respectively (HR, 0.73; 95% CI, 0.45-1.19).

In all 3 treatment groups, the median overall survival (OS) was not reached; deaths were observed in 25.3% of the combination therapy group, 25.3% of the monotherapy group, and 23.5% of the placebo group. The 36-month survival rate was 78.9% (95% CI, 73.3%-83.4%), 77.0% (95% CI, 71.3%-81.7%), and 76.6% (95% CI, 68.2%-83.0%), respectively.

“In conclusion, at this final PFS analysis, fuzuloparib improved PFS compared with placebo as maintenance therapy for patients with newly diagnosed, advanced ovarian cancer after a response to first‐line [platinum-based chemotherapy],” wrote lead study author Lingying Wu, MD, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China. “To our knowledge, this study is the first to indicate that the addition of an antiangiogenic agent (in this case, apatinib) to a PARP inhibitor (in this case, fuzuloparib) does not improve PFS among patients who have BRCA‐mutated or HRD [ovarian cancer].”

A total of 674 patients were enrolled and randomly assigned, in a 2:2:1 ratio, to either the fuzuloparib plus apatinib group (n = 269), the fuzuloparib monotherapy group (n = 269), or the placebo group (n = 136); all patients received at least 1 dose of the study treatment.

Patients were enrolled in the trial no later than 12 weeks following completion of platinum-based chemotherapy. Treatment was oral fuzuloparib at 100 mg twice daily plus oral apatinib at 375 mg once daily, fuzuloparib at 150 mg twice daily, or a matching placebo.

Eligible patients for the trial were women aged 18 to 75 years with newly diagnosed ovarian cancer, fallopian cancer, or primary peritoneal cancer who had FIGO stage III or IV disease, an ECOG performance status of 0 or 1, and adequate organ function. Additionally, they had received primary debulking surgery or neoadjuvant therapy with interval debulking surgery and 6 to 9 cycles of platinum-based chemotherapy and achieved a complete or partial response.

The primary end point of the trial was PFS per BIRC in the overall population and germline BRCA1/2-mutated subpopulation. Secondary end points included PFS by investigator, OS, best overall response, time to progression, and safety.

The median duration of treatment was 23.9 months (range, 0.1-49.7) in the fuzuloparib monotherapy group and 14.6 months (range, 0.03-39.6) in the placebo group; in the combination group, the median duration of fuzuloparib and apatinib was 23.7 months (range, 0.2-50.0) and 18.3 months (range, 0.2-50.0).

Treatment-related adverse events (TRAEs) occurred in 97.8% of the combination group, 98.9% of the fuzuloparib monotherapy group, and 94.1% of the placebo group; grade 3 or higher events occurred in 48.7%, 45.7%, and 7.4%, respectively. The most common grade 3 or higher TRAEs were anemia and hypertension in the combination group, compared with anemia, decreased platelet count, and decreased neutrophil count in the fuzuloparib monotherapy group.

Serious TRAEs occurred in 14.5%, 13.8%, and 0% of the combination, monotherapy, and placebo groups, respectively.Due to TRAEs, 14.5% of the combination group discontinued fuzuloparib and/or apatinib. In the fuzuloparib group, 8.9% discontinued treatment; 1.1% of them discontinued fuzuloparib and 8.9% discontinued apatinib placebo.

Reference

Wu L, Wang J, Li Q, et al. Fuzuloparib with or without apatinib as maintenance therapy in newly diagnosed, advanced ovarian cancer (FZOCUS-1): a multicenter, randomized, double-blind, placebo-controlled phase 3 trial. CA Cancer J Clin. 2026;76(1):e70042. doi:10.3322/caac.70042