A new poly (ADP-ribose) polymerase (PARP) inhibitor could soon be joining an already crowded treatment landscape in ovarian cancer, according to data presented at the Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women’s Cancer, which was held virtually.¹

Results of the phase III trial (ClinicalTrials.gov identifier NCT03863860) of fuzuloparib (formerly fluzoparib) as maintenance therapy in patients with platinum-sensitive, recurrent ovarian cancer showed a 7.4-month improvement in median progression-free survival (12.9 vs 5.5 months; P < .0001) and a 75.5% reduced risk of disease progression or death vs placebo (hazard ratio [HR] = 0.25).

“Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in progression-free survival for patients with platinum-sensitive relapsed ovarian cancer compared with placebo, regardless of BRCA mutation status, and had a manageable safety profile,” said presenting author, Ning Li, MD, of the Cancer Hospital of Chinese Academy of Medical Sciences.

“Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in progression-free survival for patients with platinum-sensitive relapsed ovarian cancer....”

— Ning Li, MD

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As Dr. Li reported, three PARP inhibitors (olaparib, rucaparib, and niraparib) have been approved as maintenance therapies for women with platinum-sensitive recurrent ovarian cancer in the United States and the European Union on the basis of improvements in progression-free survival from three randomized phase III trials. The Chinese trial is estimated to be completed in March 2022.

Study Design

A previous phase II study of fuzuloparib demonstrated antitumor activity in patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutations who had received between two and four prior lines of chemotherapy. The overall response rate in this phase II study was 69.9%, and the median progression-free survival was 12.0 months.²

Patients enrolled in the randomized, double-blind, phase III study had platinum-sensitive, relapsed, high-grade serous ovarian, fallopian tube, primary peritoneal, or endometrioid ovarian carcinoma (of at least grade 2) and had received at least two prior platinum-based regimens. Patients were also required to have achieved a complete or partial response to their last platinum-based regimen and had an Eastern Cooperative Oncology Group performance status of 0 or 1 at baseline.

The population was randomly assigned 2:1 to receive either 150 mg of fuzuloparib (n = 167) or placebo (n = 85) in 4-week cycles. The primary endpoint was progression-free survival, as assessed by a blinded independent central review. Key secondary endpoints included investigator-assessed progression-free survival, chemotherapy-free interval, overall survival, safety, and objective response rate for patients with measurable disease at baseline.

Principal Findings

At the time of interim analysis, the median follow-up duration was 8.5 months, and a total of 115 disease progression events had occurred. According to Dr. Li, patient characteristics were well balanced between the two groups, and BRCA mutations were confirmed in approximately 40% of patients. Additionally, said Dr. Li, nearly 25% of patients had received more than two lines of a prior platinum-based regimen, and more than half had achieved a complete response to their most recent regimen.

As of July 1, 2020, the median progression-free survival assessed by blinded independent central review was 12.9 months in the fuzuloparib group and 5.5 months in the placebo group, which met the criteria for superiority (HR = 0.25; P < .0001). Investigator-assessed progression-free survival also showed consistent improvement with fuzuloparib compared with placebo (HR = 0.27).

“In patients with or without BRCA mutation, a consistent trend of benefit was clearly demonstrated,” said Dr. Li. “In patients with different ages, different numbers of prior chemotherapy regimens, and different performance status, we saw similar trends favoring fuzuloparib. Both chemotherapy-free interval and time to disease progression also showed significant improvements with fuzuloparib compared with the placebo group.”

Safety Profile

With respect to safety, events leading to treatment interruption occurred in 40.1% of patients given fuzuloparib vs 4.8% of patients in the control group, and 24.6% of patients required dose reduction due to adverse events with fuzuloparib vs 0 patients on placebo. The most common adverse events were nausea, anemia, and other hematologic toxicities. Grade 3 or higher adverse events recorded in the intervention arm were all hematologic toxicities and included anemia (25.1%), thrombocytopenia (16.8%), and neutropenia (12.6%).

“These adverse events were manageable with treatment interruption or dose modifications, with one patient discontinuing treatment due to neutropenia,” said Dr. Li.

Additional phase III research is focusing on fuzuloparib with or without apatinib, a small-molecule, antiangiogenic drug, as first-line maintenance therapy for patients with newly diagnosed, advanced ovarian cancer, she noted. “We look forward to seeing the results of this very interesting study,” Dr. Li concluded. 

DISCLOSURE: This study is sponsored by Jiangsu Hengrui Medicine Co, Ltd. Dr. Li reported no conflicts of interest.

REFERENCES

1. Li N, Zhang Y, Wang J, et al: Fuzuloparib maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer: A multicenter, randomized, double-blind, placebo-controlled, phase III trial. Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women’s Cancer. Abstract 11557. Presented March 25, 2021.

2. Li N, Bu H, Liu J, et al: An open-label, multicenter, single-arm, phase II study of fluzoparib in patients with germline BRCA1/2 mutation and platinum-sensitive recurrent ovarian cancer. Clin Cancer Res 27:2452-2458, 2021.