"This approval is an important step forward in the treatment of ovarian cancer. In my opinion, maintenance treatment with niraparib should be considered an option for appropriate patients who responded to first-line platinum-based chemotherapy versus active surveillance."
The FDA granted approval to niraparib (Zejula) as first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.1
“PRIMA was designed for patients with ovarian cancer who have a high unmet need. The positive data observed regardless of biomarker status in this study is extremely encouraging and suggests benefit beyond the BRCA mutant population. This approval is an important step forward in the treatment of ovarian cancer. In my opinion, maintenance treatment with niraparib should be considered an option for appropriate patients who responded to first-line platinum-based chemotherapy versus active surveillance,” said Bradley Monk, MD, of US Oncology, University of Arizona College of Medicine, Phoenix Creighton University School of Medicine at St. Joseph's Hospital Phoenix, in a statement.2
Data from the phase III PRIMA study (NCT02655016) served as the basis for the approval. According to results presented at the 2020 Society for Gynecologic Oncology (SGO) Annual Meeting, niraparib led to a statistically significant improved in progression-free survival (PFS), the primary end point of the study, compared with placebo in the overall population as well as in patients with homologous recombination deficiency (HRD). In the subgroup, the median PFS was 21.9 months (range, 19.3-not evaluable [NE]) with niraparib versus 10.4 months (range, 8.1-12.1) with placebo (HR, 0.43; 95% CI: 0.31-0.59; P <.0001).
This benefit was consistent for mutational groups as well. Patients with HRD BRCA mutation showed a hazard ratio of 0.40 (95% CI, 0.27-0.62) and those with HRD BRCA wild-type had a hazard ratio of 0.50 (95% CI, 0.31-0.83).3
In the overall study population, the median PFS was 13.8 months (range, 11.5-14.9) with niraparib compared with 8.2 months (range, 7.3-8.5) with placebo (HR, 0.62; 95% CI: 0.50, 0.76; P <.0001).
In a subgroup of patients with homologous recombination proficiency, the hazard ratio was 0.68 (95% CI, 0.49-0.94).
The number of patients who experienced progressive disease (PD) or die during treatment in the niraparib arm was 86 at 6 months, 72 at 12 months, and 59 at 18 months. In the placebo, the number of patients with no PD or death was 68 at 6 months, 42 at 12 months, and 35 at 18 months.
Niraparib also demonstrated a PFS benefit across various subgroups of patients. The hazard ratio for PFS was 0.39 (95% CI, 0.23-0.66; P <.001) in patients with BRCA1 mutations and 0.35 (95% CI, 0.15-0.84; P = .0064) in patients with BRCA2 mutations.
The most common (≥10%) adverse events (AEs) reported with niraparib treatment were thrombocytopenia (39%), anemia (31%), and neutropenia (21%). Grade ≥3 treatment-related AEs occurred in 65.3% of patients in the niraparib group and 6.6% of patients in the placebo group. The most common between the niraparib and placebo groups, respectively, were anemia (31.0% vs 1.6%), thrombocytopenia (28.7% vs 0.4%), platelet count decrease (13.0% vs. 0%), and neutropenia (12.8% vs 1.2%).1-3
No new safety signals were observed in the study, Investigators did note that the emergence of grade ≥3 treatment-emergent AEs was lower among patients who were given an individualized dose of niraparib versus those who received a fixed dose of the agent. Due to toxicities, dose reduction occurred in 70.9% of patients in the niraparib arm and 12% of patients in the placebo arm. Myelosuppressive AEs were the main cause of treatment discontinuation in the study. Overall 4.3% of patients discontinued treatment as a result of thrombocytopenia.3
PRIMA is a double-blind, placebo-controlled trial that randomized 733 patients to niraparib or matched placebo. All patients included in the study were in complete response or partial response to first-line platinum-based chemotherapy. Niraparib was administered at a fixed dose of 300 mg, which was adjusted to include a lower dose of 200 mg for those weighing less than 77 kg, as well as for those with platelet counts below 150K/μL.
Of the patient included in the study about 70% had an ECOG performance status was 1, two-thirds had a FIGO stage of III, and one-third had stage IV disease. Primary tumor locations were in the ovary, fallopian tube, and peritoneum. The majority of patients had serous histology (~95%). Most patients had achieved a complete response to prior chemotherapy (70%). Neoadjuvant chemotherapy was received by two-thirds of patients and no participants had received prior bevacizumab (Avastin).
The FDA did not require an FDA-approved companion diagnostic for initiation of treatment with niraparib.
1. FDA approves niraparib for first-line maintenance of advanced ovarian cancer [new release]. FDA website. April 29, 2020. https://bit.ly/3f7rNKS. Accessed April 29, 2020.
2. FDA approves Zejula (niraparib) as the only once-daily PARP inhibitor in first-line monotherapy maintenance treatment for women with platinum-responsive advanced ovarian cancer regardless of biomarker status [news release]. London, United Kingdom: GlaxoSmithKline plc; April 29, 2020. https://bit.ly/35hrVTc. Accessed April 29, 2020.
3. Bradley, MJ. Efficacy of niraparib therapy in patients with newly diagnosed advanced ovarian cancer by BRCA and homologous recombination status: PRIMA/ENGOT-OV26/GOG-3012 study. Presented at the 2020 Society of Gynecologic Oncology Virtual Annual Meeting; April 29, 2020.