In patients with newly diagnosed advanced ovarian cancer at high risk of recurrence, there was no difference in overall survival with first-line maintenance niraparib as compared to placebo. In the HRD population, patients alive at 5 years were twice as likely to be progression-free with niraparib treatment than with placebo.
Previously, the phase III PRIMA trial met its primary endpoint, demonstrating that niraparib first-line maintenance significantly extended progression-free survival (PFS) in patients with advanced ovarian cancer that responded to first-line platinum-based chemotherapy in the homologous recombination-deficient (HRD) and overall populations. At ESMO 2024, the final planned overall survival (OS) and updated ad hoc PFS results were presented.
In the international, randomised, double-blind, placebo-controlled phase III PRIMA trial, patients with newly diagnosed, advanced ovarian cancer were randomised 2:1 to maintenance treatment with niraparib or placebo. Previously, these patients’ tumours had shown a complete or partial response to first-line treatment with platinum-containing chemotherapy. Patients were treated once daily for 36 months or until disease progression. The primary outcome was PFS, with OS begin the key secondary endpoint. In addition, the long-term safety of the treatments was determined and an updated ad hoc analysis of PFS was performed.
A total of 733 patients were randomised (median age: 62 years) to niraparib (N= 487) or placebo (N= 246). After a median follow-up of 73.9 months, there was no difference in OS between niraparib and placebo arms in the overall, HRD and HRP populations. In the niraparib group, the overall median OS was 46.6 months, as compared to 48.8 months with placebo, with 5-year OS rates of 42% and 44%, respectively (HR[95%CI]: 1.01[0.84-1.23], p= 0.8834). In the HRD population, 5-year OS was 55% with niraparib and 56% with placebo (HR[95%CI]: 0.95[0.70-1.29]), and 29% and 27%, respectively in the HRP population (HR[95%CI]: 0.93[0.69-1.26]). This lack of OS benefit might be explained by the 3-fold higher subsequent PARP inhibitor use in the placebo arm as compared to the niraparib arm across populations.
However, the niraparib PFS benefit was sustained with additional follow-up in both the overall and HRD populations. In the overall study population, 5-year PFS was 22% in the niraparib group compared to 12% in the placebo group (HR[95%CI]: 0.66[0.55-0.78]). In the HRD- population this was 35% versus 16% (HR[95%CI]: 0.51[0.40-0.66]), and in the HRP-negative population 8% versus 7%, respectively (HR[95%CI]: 0.67[0.50-0.89]).
Finally, the long-term safety remained consistent with the established safety profile of niraparib. The incidence of myelodysplastic syndrome or acute myeloid leukemia was 2.3% in the niraparib group versus 1.6% in the placebo group. No new safety signals were observed.
The international, randomised, placebo-controlled phase III trial PRIMA has shown that patients with newly diagnosed, advanced ovarian cancer experience no survival benefit after almost 74 months when treated with niraparib, compared to placebo. However, patients treated with niraparib were approximately twice as likely to be free of disease progression after 5 years. This long-term safety analysis revealed no new safety signals for niraparib treatment.
Reference
González-Martin A, et al. Final overall survival (OS) in patients (pts) with newly diagnosed advanced ovarian cancer (aOC) treated with niraparib (nir) first-line (1L) maintenance: results from PRIMA/ENGOT-OV26/GOG-3012. Presented at ESMO 2024; Abstract LBA29.
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