First-line Niraparib Improves PFS in Ovarian Cancer

Ning Li, MD

An individualized starting dose of niraparib (Zejula), determined by weight and platelet count, continued to demonstrate a clinical meaningful improvement in progression-free survival (PFS) in newly diagnosed ovarian cancer in the first-line maintenance setting, regardless of biomarker status, according to data from the phase 3 PRIME study (NCT03709316) presented during the 2022 SGO Annual Meeting on Women’s Cancer.

The median PFS in the intent-to-treat (ITT) population was 24.8 months (HR, 0.45; 95% CI, 19.2–not estimated [NE]) in the nirapa- rib arm compared with 8.3 months (95% CI, 7.3-11.1) in the placebo group (HR, 0.45; 95% CI, 0.34-0.60; P < .001). The homologous recombination deficiency (HRD) subgroup had a median PFS that was not reached (NR; 95% CI, 22.3-NE) in the niraparib arm vs 11.0 months (95% CI, 8.3-13.8) in the placebo group (HR, 0.48; 95% CI, 0.34-0.68; P <.001).

Patients with BRCA mutations had a median PFS that was NR (95% CI, 22.3-NE) vs 10.8 months (95% CI, 8.3-19.3) in the niraparib and placebo cohorts, respectively (HR, 0.40; 95% CI, 0.23-0.68; P < .001). Those with non–germline BRCA (non-gBRCA) mutations had a median PFS of 19.3 months (95% CI, 13.8-NE) vs. 8.3 months (95% CI, 5.6-11.2) in the niraparib and placebo groups, respectively (HR, 0.48; 95% CI, 0.34-0.67; P < .001).

In the non-gBRCA mutation subgroups, those who were HRD had a median PFS of 24.8 months (95% CI, 14.0-NE) vs 11.1 months (95% CI, 8.3-13.8) in the niraparib and placebo groups, respectively (HR, 0.58; 95% CI, 0.36-0.93; P = .022).

For those with non–gBRCA mutations who were homologous recombination proficient, the median PFS was 14.0 months (95% CI, 11.9-NE) vs 5.5 months (95% CI, 2.9-7.3) in the niraparib and placebo groups, respectively (HR, 0.41; 95% CI, 0.25-0.65; P < .001).

“PRIME data continue to support niraparib monotherapy after first-line platinum-based chemotherapy regardless of biomarker status,” Ning Li, MD, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, said during the presentation.

A total of 384 patients were randomized 2:1 and received either niraparib (n = 255) or placebo (n = 129) for 36 months or until disease progression, death, or unacceptable toxicity. Patients were eligible for treatment if they had FIGO stage III or IV ovarian cancer, a high-grade or serous endometrioid tumor, previous primary or interval cytoprotective surgery despite postoperative residual disease status, and a complete (CR) or partial response (PR) to first-line platinum-based chemotherapy.

Stratification factors included germline BRCA mutational status, tumor HRD status, previous neoadjuvant chemotherapy, and response to first-line platinum chemotherapy. The primary end point was PFS via blinded independent central review in the ITT population. Secondary end points were OS, time to first subsequent anti- cancer therapy in the ITT subgroup, PFS and OS in the HRD subgroup, and safety.

At data cut-off, 102 patients in the niraparib group and 29 in the placebo were still receiving treatment. The median follow-up was 27.5 months.

Patient characteristics included a median age of 53.0 years in the niraparib group vs 54.0 years in the placebo, and a median weight of 59.0 kg in the niraparib group and 57.0 kg in the placebo group. A total of 71.4% of patients in the niraparib group had FIGO stage III disease vs 72.9% in the placebo and 28.6% vs 27.1% of patients in both respective groups had stage IV disease.

A total of 83.1% and 79.8% experienced a CR to previous platinum-based chemotherapy in the niraparib and chemotherapy groups, respectively. Prior treatment with chemotherapy resulted in a PR in 16.9% vs 20.2% of patients in each respective group. A total of 33.3% of patients in the niraparib group and 31.0% in the placebo group had a germline BRCA mutation.

At 24 months, 52.6% in the niraparib group and 30.4% in the placebo group did not have progressive disease or death. Those in the HRD subgroup without progressive disease or death included 57.4% in the niraparib group and 33.9% in the placebo group.

OS data were immature in the ITT population (HR, 0.63; 95% CI, 0.38-1.03; P = .061). The median time to first subsequent anti-cancer therapy was 29.2 months (95% CI, 22.4–NE) in the niraparib group and 11.9 months (95% CI, 8.8-14.8) in the placebo group.

"While overall survival [OS] data are still immature, there is a trend in favor of niraparib at this data cut-off,” Li said.

Grade 3 or higher treatment-emergent adverse events (TEAEs) were observed in 54.5% vs 17.8% of patients in the niraparib and placebo groups, respectively. Grade 3/4 treatment-related AEs were observed in 49.0% vs 7.0% in the niraparib and placebo groups, respectively. Serious TEAEs were observed in 18.8% vs 8.5% of patients in the niraparib and placebo groups, respectively, of which 14.9% vs 3.9% treatment related (TABLE1).

In the niraparib and placebo cohorts, TEAEs relating to treatment interruption were observed in 62.7% vs 19.4%, dose reductions in 40.4% vs 6.2%, discontinuation in 6.7% vs 5.4%, and death in 0.4% vs 0% of patients, respectively. Common grade 3 or higher TEAEs observed in the niraparib and placebo cohorts, respectively, were decreased neutrophil count (17.3% vs 1.6%), decreased white blood cell count (6.7% vs 0.8%), anemia (18.0% vs 1.6%), decreased platelet count (14.1% vs 0.8%), and increased glutamyltransferase (5.1% vs 17.1%).

_REFERENCE

_{Li N, Zhu J, Yin R, et al. Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): a randomized, double-blind, placebo-controlled, phase 3 trial. Presented at: 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022; Phoenix, AZ.}