First-line niraparib maintenance regimen boosts PFS in advanced ovarian cancer

First-line maintenance therapy with niraparib at an individualized starting dose (ISD) improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer, according to results of the phase III PRIME study presented at SGO 2022.

Participants were 384 adults with FIGO stage III–IV ovarian cancer and high-grade serous or endometrioid tumours. They had received primary or interval cytoreductive surgery and had complete or partial response to first-line platinum-based chemotherapy. They were randomized 2:1 to receive oral niraparib (n=255; median age 53 years) or placebo (n=129; median age 54 years) at an ISD of 200 mg QD (300 mg for patients with body weight ≥77 kg and platelet count ≥150,000/µL) for 36 months or until disease progression or unacceptable toxicity.

The patients were followed up for a median 27.5 months, with 102 and 29 patients in the niraparib and placebo groups, respectively, still on treatment at data cut-off. Most patients were FIGO stage III (71–73 percent) and had complete response to chemotherapy (80–83 percent), 99.2 percent had serous tumours, about one-third had gBRCA mutations, and two-thirds were homologous recombination deficient.

PFS* in the intention-to-treat (ITT) population was significantly improved by 16.5 months with niraparib vs placebo (median 24.8 vs 8.3 months; hazard ratio [HR], 0.45, 95 percent confidence interval [CI], 0.34–0.60; p<0.001). At 24 months, 52.6 percent of niraparib recipients did not experience progression or death compared with 30.4 percent of placebo recipients. [SGO 2022, abstract LBA 5]

The results were consistent in multiple subgroups analysed including age, receipt of neoadjuvant chemotherapy, response to platinum-based chemotherapy, homologous recombination deficiency or proficiency, and postoperative residual disease status.

A prespecified subgroup analysis indicated that the PFS benefit with niraparib vs placebo was also evident regardless of the presence or absence of gBRCA mutations (median not reached [NR] vs 10.8 months; HR, 0.40, 95 percent CI, 0.23–0.68; p<0.001 for gBRCAmut and median 19.3 vs 8.3 months; HR, 0.48, 95 percent CI, 0.34–0.67; p<0.001 for non-gBRCAmut).

Among patients without gBRCA mutation, niraparib also improved PFS compared with placebo regardless of whether patients were homologous recombination deficient (median 24.8 vs 11.1 months; HR, 0.58, 95 percent CI, 0.36–0.93; p=0.022) or proficient (median 14.0 vs 5.5 months; HR, 0.41, 95 percent CI, 0.25–0.65; p<0.001). In the total homologous recombination deficient subgroup, PFS was also significantly improved with niraparib vs placebo (median NR vs 11.0 months; HR, 0.48, 95 percent CI, 0.34–0.68; p<0.001), with 57.4 and 33.9 percent of niraparib and placebo recipients, respectively, remaining event-free at 24 months.

Overall survival was immature at data cut-off (16.9 percent maturity) but demonstrated a trend toward improvement with niraparib over placebo (median NR in both groups; HR, 0.63; p=0.061). Time to first subsequent cancer treatment was significantly extended with niraparib vs placebo (median 29.2 vs 11.9 months; HR, 0.45, 95 percent CI, 0.34–0.59; p<0.001).

Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in more niraparib than placebo recipients (54.5 percent vs 17.8 percent), with 49 and 7 percent, respectively, deemed treatment related. Serious treatment-related TEAEs were reported in 14.9 and 3.9 percent, respectively. TEAEs led to treatment interruption in 62.7 and 19.4 percent, respectively, dose reduction in 40.4 and 6.2 percent, and discontinuation in 6.7 and 5.4 percent, respectively. TEAEs led to death in one niraparib and no placebo recipients.

The most common (≥20 percent) grade ≥3 TEAEs in the niraparib group were anaemia, decreased neutrophil count, and decreased platelet count (18.0, 17.3, and 14.1 percent, respectively). There was one case each of acute myeloid leukaemia (AML) and myelodysplastic syndrome in the niraparib group, with the case of AML leading to death. 

“TEAEs were manageable and consistent with the PARP** inhibitor class [and] no new safety signals were identified for niraparib,” remarked study author Dr Ning Li from the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

“[In addition,] dose reduction in all patients was numerically lower than in the previous niraparib trials using fixed starting dosing.”

“PRIME data continue to support niraparib monotherapy as standard of care after first-line platinum-based chemotherapy regardless of biomarker status,” Li concluded.