Niraparib significantly extends PFS in newly diagnosed advanced ovarian cancer
BARCELONA, Spain — Niraparib significantly extended PFS among women with newly diagnosed advanced ovarian cancer, according to results of the randomized phase 3 PRIMA study presented at European Society for Medical Oncology Congress.
Researchers observed the benefit in the entire population regardless of homologous recombination deficiency status.
“Based on these results, niraparib monotherapy after first-line platinum-based chemotherapy should be considered a new standard of care,” Antonio Gonzalez-Martin, MD, co-director of the department of medical oncology at Clinica Universidad de Navarra in Spain, said during his presentation.
Up to 85% of women with advanced ovarian cancer experience disease recurrence after first-line platinum-based chemotherapy. Options for maintenance therapy often are limited to select patient populations, and many women undergo watchful waiting after chemotherapy, according to study background.
Niraparib (Zejula, Tesaro/GlaxoSmithKline) is the first poly(ADP-ribose) polymerase (PARP) inhibitor to receive FDA approval as maintenance therapy for all women with recurrent ovarian cancer regardless of BRCA mutation status.
Gonzalez-Martin and colleagues conducted the double-blind, placebo-controlled PRIMA study to evaluate the efficacy and safety of niraparib for all women with newly diagnosed advanced ovarian cancer — again, regardless of BRCA status — who achieved complete or partial response to first-line platinum chemotherapy but were at high risk for recurrence.
Women with stage III disease who had complete cytoreduction, meaning no visible residual disease, after primary debulking surgery were excluded.
The analysis included 733 women with high-grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer.
Researchers randomly assigned 487 women to niraparib dosed at either 200 mg or 300 mg daily based on body weight. The other 246 women received placebo.
Half of the women in each treatment group were positive for homologous recombination deficiency. Overall, 35% of women had stage IV disease, 67% received neoadjuvant chemotherapy and 31% achieved partial response to first-line chemotherapy.
PFS as assessed by blinded independent central review served as the primary endpoint. Investigators used hierarchical testing to evaluate PFS, starting with women who had homologous recombination-deficient tumors — as determined by the MyChoiceHRD test (Myriad Genetics) — and then evaluating the overall population. Homologous recombination deficiency equated to tissue test score of at least 42 or presence of a BRCA mutation.
OS served as a key secondary endpoint. Other secondary endpoints included PFS2, time to first subsequent therapy, patient-reported outcomes and safety.
The final analysis included 728 women, nearly 51% of whom had homologous recombination deficiency.
Results showed niraparib significantly extended median PFS compared with placebo in the homologous recombination deficiency-positive subgroup (21.9 months vs. 10.4 months; HR = 0.43; 95% CI, 0.31-0.59), with higher percentages of niraparib-treated women remaining progression free at 6 months (86% vs. 68%), 12 months (72% vs. 42%) and 18 months (59% vs. 35%).
Niraparib also significantly extended median PFS in the overall study population (13.8 months vs. 8.2 months; HR = 0.62; 95% CI, 0.5-0.75), with a consistent PFS benefit at 6 months (73% vs. 60%), 12 months (53% vs. 35%) and 18 months (42% vs. 28%).
Investigators observed “a sustained and durable treatment effect” in all patient subgroups.
Niraparib conferred comparable clinical benefit for homologous recombination deficient women with BRCA mutations (HR = 0.4; 95% CI, 0.27-0.62) or with BRCA wild type disease (HR = 0.5; 95% CI, 0.31-0.83), as well as for women with homologous recombination-proficient disease (HR = 0.68; 95% CI, 0.49-0.94).
Women at the highest risk for early disease progression — including those who received neoadjuvant chemotherapy and those who achieved partial response to first-line platinum chemotherapy — derived significant benefit, Gonzalez-Martin said.
OS data were immature at the time of data cutoff, with only 11% of events occurring.
No new safety signals emerged, Gonzalez-Martin said.
Women assigned niraparib were more likely to experience any treatment-emergent adverse event (98.8% vs. 91.8%), or grade 3 or higher events (70.5% vs. 18.9%). The most common grade 3 or higher adverse events among niraparib-treated patients were anemia (31%), thrombocytopenia (29%) and neutropenia (13%). No treatment-related deaths occurred.
Higher percentages of women assigned niraparib discontinued treatment due to adverse events (12% vs. 2.5%), experienced adverse events that required dose reductions (70.9% vs. 8.2%) or required dose interruptions due to adverse events (79.5% vs. 18%).
“Niraparib is the first PARP inhibitor to demonstrate benefit [for] patients across biomarker subgroups after platinum-based chemotherapy in [the front-line setting], consistent with prior clinical studies of niraparib in recurrent ovarian cancer,” Gonzalez-Martin said. “No new safety signals were observed, and quality of life was maintained.” – by Mark Leiser
Reference: Martin AG, et al. Abstract LBA1. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.
Disclosures: Tesaro funded this study. Gonzalez Martin reports consultant/advisory roles with, speaker bureau roles with, expert testimony for, research grants or funding from, and travel, accommodations or expenses from AstraZeneca, Clovis Oncology, Genmab, ImmunoGen, Merck, Merck Sharpe & Dohme, Oncoinvent, Pfizer, PharmaMar, Roche and Tesaro. Please see the abstract for all other authors’ relevant financial disclosures.