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Niraparib Improves Progression-Free Survival in Advanced Ovarian Cancer, Regardless of Subgroup

Conference Correspondent

Treatment with niraparib led to improved progression-free survival (PFS) in an entire population of patients with advanced ovarian cancer, regardless of biomarker status. This improvement was evidenced by a significant 38% reduction in the risk of cancer recurrence or death due to any cause in patients treated with the drug, with no new safety signals identified. These findings come from the phase 3 PRIMA study, presented by Bradley J. Monk, MD, at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

“Niraparib monotherapy could be considered as a new opportunity after first-line platinum-based chemotherapy,” he reported.

Niraparib has previously demonstrated improved PFS in patients with newly diagnosed advanced ovarian cancer after first-line platinum-based chemotherapy, including patients at highest risk of relapse. In an exploratory analysis of the PRIMA study, Dr Monk, from Arizona Oncology (US Oncology Network), and colleagues sought to evaluate the efficacy of niraparib according to patient biomarker subgroups.

The double-blind, placebo-controlled trial included 733 patients with newly diagnosed advanced ovarian, primary peritoneal, or fallopian tube cancer who had demonstrated a complete or partial response (CR/PR) to first-line platinum-based chemotherapy.

Stratification factors were best response to first-line chemotherapy (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination status (deficient/proficient/not determined). The primary end point of PFS, assessed by blinded independent central review, was tested in homologous recombination-deficient (HRd) patients, then in the overall population. Median follow-up was 13.8 months.

In total, 728 patients received intervention, 370 of whom were HRd. A total of 484 patients were randomized to niraparib (245 HRd), and 244 were randomized to placebo (125 HRd) once daily.

Overall, 51% of patients were HRd and 34% were homologous recombination-proficient (HRp); 35% had stage IV disease, 67% received neoadjuvant chemotherapy, 30% had BRCA-mutated tumors and 31% had a PR to first-line platinum-based chemotherapy.

Exploratory analysis showed a consistent treatment effect among all relevant subgroups; niraparib-treated patients in all biomarker groups had a statistically significant and clinically meaningful PFS benefit, with an almost 40% risk reduction. As previously reported, in HRd patients, there was a clinically significant 57% reduction in the risk of cancer recurrence or death.

Importantly, niraparib efficacy was similar in patients with BRCA1 and BRCA2 mutations.

“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.”

Niraparib also provided clinical benefit in the HRd and HRp subgroups; there was a consistent treatment effect with hazard ratios of 0.40, 0.50, and 0.68 in the HRd BRCA-mutant, HRd BRCA-wildtype, and HRp subgroups, respectively.

The most common grade ≥3 adverse events were anemia in 31% of patients, thrombocytopenia in 29%, and neutropenia in 13%. Dr Monk noted that after the trial had enrolled about two-thirds of patients, dosing was individualized for the last one-third of patients who enrolled. The incidence of grade ≥3 hematologic treatment-related adverse events was lower in patients who received an individualized dose of niraparib compared with patients who received a fixed dose.

“With the individualized dose, thrombocytopenia went from 36% to 15%,” he said. “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.”

According to these findings, the investigators conclude that patients with ovarian cancer at the highest risk of early disease progression can benefit significantly and statistically from niraparib treatment.

SGO 2020 Annual Meeting on Women’s Cancer. Abstract 31. Presented April 29, 2020.

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