Niraparib maintenance prolongs PFS in advanced ovarian cancer

Maintenance therapy with niraparib significantly extends progression-free survival (PFS) compared with placebo in patients with newly diagnosed advanced ovarian cancer who responded to treatment with first-line platinum-based chemotherapy, according to the PRIME* trial.

In the intention-to-treat (ITT) population, patients treated with niraparib achieved a significantly reduced risk of disease progression or death by 55 percent compared with placebo (median PFS, 24.8 vs 8.3 months; hazard ratio [HR], 0.45; p<0.001).

“The treatment outcome with niraparib appeared to be better in PRIME than in PRIMA** study, as demonstrated by the much longer median PFS with niraparib (24.8 vs 13.8 months),” according to the researchers.

The phase III PRIME study included 384 patients (median age 54 years) with newly diagnosed advanced ovarian cancer who were recruited from 29 hospitals in China. Participants were randomized to receive oral niraparib (n=255), with an individualized starting dose (ISD) of 200 mg based on body weight (<77 kg) and/or platelet count (<150 x 10³/µL), or placebo (n=129) once daily. Patients were treated for 36 months or until disease progression, intolerable toxicity, death, withdrawal of consent, or loss to follow up. [JAMA Oncol 2023;doi:10.1001/jamaoncol.2023.2283]

Participants were stratified by tumour homologous recombination deficiency (HRD) and germline BRCA variant status.

Among patients with tumour HRD, the median PFS, as assessed by BICR***, was not reached in the niraparib group and was 11.0 months in the placebo group (HR, 0.48).

A longer median PFS was observed in homologous recombination-proficient and -indeterminate patients treated with niraparib than those on placebo (16.6 vs 5.5 months; HR, 0.41 and 13.8 vs 5.4 months; HR, 0.36, respectively).

A PFS benefit was also observed with niraparib vs placebo among a subgroup of patients with (median, not reached vs 10.8 months; HR, 0.40) and without (median 19.3 vs 8.3 months; HR, 0.48) germline BRCA­ mutations.

“Niraparib in the current study afforded PFS benefit vs placebo regardless of biomarker status, which was consistent with the findings from PRIMA,” the researchers noted.

Among patients who underwent debulking surgery, those in the niraparib group achieved a significantly extended median PFS than those in the placebo group (median 24.8 vs 8.3 months; HR, 0.44 [optimal] and 16.5 vs 8.3 months; HR, 0.27 [suboptimal]).

In terms of safety, grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 54.5 percent of patients on niraparib and 17.8 percent of patients on placebo.

Anaemia (18.0 percent) and decreased neutrophil count (17.3 percent), platelet count (14.1 percent), and white blood cell count (6.7 percent) were the most frequently reported TEAEs in the niraparib group.

“Nevertheless, most TEAEs were well controlled, which led to low treatment discontinuation in both groups (6.7 percent [niraparib] vs 5.4 percent [placebo],” said the researchers.

Of note, grade ≥3 TEAEs and treatment discontinuation resulting from TEAEs were reported much less frequently in niraparib-treated patients from PRIME than in their counterparts from PRIMA, the researchers noted.

“These results indicate that ISD can lead to better safety and tolerability profiles of niraparib than a fixed starting dose at 300 mg once daily and further support the use of ISD in clinical practice,” they said.

“Overall, the PRIME randomized clinical trial prospectively demonstrated that as maintenance therapy, niraparib with ISD significantly prolonged PFS vs placebo in the ITT population with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, irrespective of postoperative residual disease status or biomarker status,” said the researchers.