Niraparib maintenance yields favourable OS trend in patients with ovarian cancer

Maintenance treatment with niraparib, a potent, highly selective PARP* inhibitor, provides a favourable overall survival (OS) trend compared with placebo in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC), regardless of germline BRCA (gBRCA) mutation status, according to the final analysis of the NORA trial presented at SGO 2024.

This final OS analysis was conducted after OS events occurred in ≥50 percent of the intention-to-treat (ITT) population, with the OS data reaching a maturity rate of 52 percent, said lead author Dr Xiaohua Wu from Fudan University Shanghai Cancer Center in Shanghai, China.

At a median follow-up of 57.9 months, patients treated with niraparib achieved a longer median OS than those treated with placebo in the ITT population (51.5 vs 47.6 months; hazard ratio [HR], 0.86).

An OS trend favouring niraparib over placebo was also observed in the subgroup of patients with gBRCA (median 56.0 vs 47.6 months; HR, 0.86) and non-gBRCA (46.5 vs 46.9 months; HR, 0.87) mutations.

Wu stressed that the OS trend favoured niraparib despite that a greater percentage of patients in the placebo arm received ≥1 dose of subsequent PARP inhibitory treatment in either the gBRCA or non-gBRCA cohorts (57.1 percent and 39.65 percent, respectively).

“[Overall, the current study] demonstrated a favourable OS trend with niraparib using ISD** vs placebo as maintenance therapy in patients with PSROC, regardless of gBRCA mutation status. [This was] despite 46.6 percent of patients [ITT cohort] in the placebo group receiving ≥1 dose of subsequent PARP inhibitor therapy,” said Wu.

This phase III NORA trial included 265 Chinese patients with PSROC who had completed ≥2 prior platinum-containing chemotherapy lines and achieved a complete or partial response to the last platinum-based chemotherapy. Participants were randomized in a 2:1 ratio to receive either niraparib (n=177) or placebo (n=88). Niraparib was given with an ISD of 200 mg once daily for patients with baseline body weight <77 kg or platelet count <150 x 10³/µL and 300 mg for those above these thresholds.

Other secondary endpoints

In the ITT cohort, those on niraparib experienced a longer chemotherapy-free interval (CFI; median 19.7 vs 10.1 months; HR, 0.47) and time-to-first subsequent anticancer therapy (TFST; median 16.6 vs 7.7 months; HR, 0.39) than those on placebo.

Longer median progression-free survival 2 (PFS2) was also observed in the niraparib group than in the placebo group (27.5 vs 17.3 months; HR, 0.52).

Consistent with the ITT population, treatment with niraparib also demonstrated favourable results vs placebo in terms of CFI, TFST, and PFS2, both in patients with gBRCA (HRs, 0.34, 0.34, and 0.33, respectively) and non-gBRCA (HRs, 0.56, 0.43, and 0.67) mutations.

Adverse events

Three patients in the niraparib group developed myelodysplastic syndrome/acute myeloid leukaemia, while none were reported in the placebo group.

Wu noted that at long-term follow-up, niraparib treatment did not reveal any new safety signals.

“Demonstrating a clinically important and statistically significant improvement in PFS [in the previous study] and a favourable OS trend with niraparib vs placebo [in the current study], the phase III NORA trial continues to support the use of niraparib maintenance therapy with ISD for patients with PSROC, regardless of gBRCA mutation status,” Wu noted.