Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study

Abstract

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.

Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs).

Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively.

Conclusion: The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Trial registration: ClinicalTrials.gov Identifier: NCT03759600.

Keywords: Clinical Trial, Phase II; Ovarian Cancer; Poly(ADP-ribose) Polymerase Inhibitors.

Fig. 1. Tumor responses. (A) Waterfall plot of ORR in the FAS. Includes all patients who had evaluable post-baseline target lesion(s). Tumor BRCA1/2 mutation status is dichotomized as ‘positive’ or ‘negative’ (includes ‘unknown’). The individual bars show the reduction rate at the time when the sum of the target lesion size decreased the most after starting administration of niraparib for each patient. The best overall response based on RECIST v1.1 shown at the end of each bar takes into account not only changes in the size of target lesions, but also evaluation of non-target lesions and the presence or absence of new lesions. (B) Change from baseline in target lesion size over time.

CR, complete response; FAS, full analysis set; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; SoD, sum of diameters.

Fig. 2. Kaplan–Meier plot of duration of response in responders.

Fig. 3. Kaplan–Meier plot of (A) PFS and (B) OS in the FAS.

FAS, full analysis set; OS, overall survival; PFS, progression-free survival.