Niraparib maintenance boosts PFS in advanced ovarian cancer

Maintenance therapy with the PARP* inhibitor niraparib led to a sustained and durable progression-free survival (PFS), regardless of biomarker status,  in patients with primary advanced ovarian cancer who responded to platinum-based chemotherapy,  an updated analysis of the phase III PRIMA/ENGOT-OV26/GOG-3012 trial has shown.

At a median follow-up of 3.5 years (data cut-off November 17, 2021), the median investigator-assessed PFS more than doubled with niraparib at 24.5 months vs 11.2 months with placebo in the homologous recombination deficiency (HRD) population (n=373; hazard ratio [HR], 0.52, 95 percent confidence interval [CI], 0.40–0.68; p<0.001). [ESMO 2022, abstract 530; Ann Oncol 2022;33(suppl 7):S235-S282.doi:10.1016/annonc/annonc1054]

In the overall population (n=733), the median investigator-assessed PFS was 13.8 months with niraparib vs 8.2 months with placebo (HR, 0.66, 95 percent CI, 0.56–0.79; p<0.001).

Clearly, treatment with niraparib boosted PFS vs placebo across the biomarker subgroups analysed. The biggest benefit was in patients with BRCA-mutated HRD tumours (HR, 0.45, 95 percent CI, 0.32–0.64).

“Niraparib benefits were sustained in the long term, with hazard ratios consistent with the primary analysis regardless of biomarker status,” commented lead study author Dr Antonio González-Martin, Medical Oncology Department, Clinica Universidad de Navarra in Pamplona, Navarra, Spain. “There was a clinically meaningful 48-percent and a 35-percent reduction in the risk of disease progression or death in the HRD and homologous recombination–proficient [HRp] populations, respectively.”

A look at the PRIMA population

The patients had newly diagnosed ovarian cancer and were at high risk for recurrence following response to frontline platinum-based chemotherapy. They were randomly assigned 2:1 to receive niraparib (n=487) or placebo (n=246) within 12 weeks of receiving their last cycle of chemotherapy.

At the start of the trial, niraparib was administered at a fixed dose of 300 mg and was reduced to 200 mg in patients who weighed <77 kg or with platelet counts <150K/μL. Treatment was for 36 months or until disease progression.

Primary and secondary outcomes

The primary endpoint was PFS by blinded independent central review (BICR) in the HRD and the overall population. Secondary endpoints were overall survival (OS), time to second disease progression, time to first subsequent therapy, patient-reported outcomes, and safety.

In the primary analysis, niraparib significantly improved PFS per BICR over placebo (21.9 months vs 10.4 months; HR for disease progression or death, 0.43, 95 percent CI, 0.31–0.59; p<0.001).  The PFS in the overall population was longer with niraparib. [N Engl J Med 2019; 381:2391-2402]

The findings supported niraparib approval in the US for maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to frontline platinum-based chemotherapy, regardless of biomarker status. [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer; accessed October 4, 2022]

ESMO 2022 update

In the updated data released at ESMO 2022, the 1-year PFS rate in the HRD population was 70 percent with niraparib vs 47 percent with placebo. Two-year PFS rates were 51 percent and 29 percent, respectively. The 3-year rates were 44 percent vs 23 percent, while the 4-year rates were 38 percent and 17 percent, respectively.

The 1-year PFS rate in the overall population was 54 percent with niraparib vs 39 percent with placebo. At 2 years, these were 36 percent vs 22 percent, respectively. Three-year rates were 29 percent vs 18 percent, respectively, and  4-year rates were 24 percent vs 14 percent, respectively.

In patients with BRCA wild-type HRD tumours, the hazard ratio (HR) for PFS was 0.66 whereas 0.65 in those with HRp tumors. Data remained immature for the overall population at 41.2 percent.

Over 9 percent of those treated with niraparib and 33.3 percent of those given placebo received subsequent PARP inhibitor therapy during follow-up. There were no new safety signals. The treatment discontinuation rate due to toxicity was low.

Eleven patients discontinued niraparib because of treatment-emergent adverse effects (TEAEs). However, TEAEs that led to dose interruptions and reductions were both reduced with individualized starting doses. Deaths due to TEAEs were not drug related.