Niraparib monotherapy may represent a new opportunity after first-line platinum-based chemotherapy in the treatment of advanced ovarian cancer, based on an updated analysis of the phase 3 PRIMA study presented at the 2020 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
The exploratory analysis showed that treatment with niraparib (Zejula) improved progression-free survival (PFS) in patients regardless of their biomarker status.
In the analysis, patients who received niraparib in all biomarker groups had a statistically significant and clinically meaningful PFS benefit, with an overall 38% reduction in the risk for a progression event (hazard ratio [HR], 0.62; P <.0001). In patients with homologous recombination deficiency, as reported previously, the risk for cancer recurrence or death was reduced by 57% in patients who received niraparib compared with placebo (P <.0001).
Niraparib previously demonstrated an improvement in PFS in patients with newly diagnosed advanced ovarian cancer after first-line platinum-based chemotherapy, including patients at the highest risk for relapse. In the exploratory analysis of PRIMA presented, Bradley J. Monk, MD, FACOG, FACS, Gynecologic Oncologist, Arizona Oncology (US Oncology Network), Phoenix, and colleagues evaluated the efficacy of niraparib according to biomarker subgroups.
The PRIMA clinical trial enrolled 733 patients with newly diagnosed advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response to first-line platinum-based chemotherapy. They were randomized in a 2:1 ratio to niraparib or placebo once daily.
After the trial had enrolled nearly two-thirds of patients, niraparib dosing was individualized for the remaining patients enrolled.
Of the 733 patients randomized, 373 (51%) had homologous recombination deficiency and 249 (34%) had homologous recombination proficiency.
In the subset of patients with BRCA mutations, niraparib reduced the risk for progression by 60% (HR, 0.40; P <.0001), and in those with BRCA wild-type, the reduction in risk was 50% (HR, 0.50; P = .0064).
Niraparib efficacy for PFS was similar in patients with BRCA1 mutations (HR, 0.39; 95% confidence interval [CI], 0.23-0.66) and BRCA2 mutations (HR, 0.35; 95% CI, 0.15-0.84).
The rate of dose modifications and the safety profile were similar to data reported in earlier trials of niraparib. The researchers reported that no new safety signals were identified in the current trial.
“I think all of us recognize that BRCA1 mutations are about twice as common as BRCA2. We realize that BRCA1 is more pathogenic, meaning the risk of breast and ovarian cancer is higher, and we also realize that BRCA1 patients are harder to treat with a PARP inhibitor,” said Dr Monk. “In this hypothesis-generating exploratory analysis, there was a consistent treatment effect in the BRCA1 and BRCA2 patients. This is an important new piece of information.”
In addition to the significant benefit on PFS in the homologous recombination-deficient subgroup, niraparib also provided a 32% reduction in the risk for a PFS event (HR, 0.68; P = .0203) in the homologous recombination-proficient subgroup.
After dosing of niraparib was individualized, the rate of grade ≥3 thrombocytopenia in the niraparib arm decreased from 36% to 15%, said Dr Monk. “So, there’s an opportunity here to individualize the dose based on weight and baseline platelet count. We have not shown the impact of outcomes for this, but stay tuned.”