Niraparib (2) – Zejula®

• Clinical trials
  • The NOVA trial is a multicentre, randomised, double-blind, controlled Phase III trial in which niraparib is compared with placebo in two independent cohorts.
  • Study 19 is a multicentre, double-blind, randomised, controlled trial comparing olaparib with placebo.
  • The SOLO2 study is a multicentre, double-blind, randomised, controlled trial comparing olaparib with placebo.

Adult female patients with recurrent platinum-sensitive, poorly differentiated serous carcinoma of the ovaries or fallopian tubes, or with primary peritoneal carcinomatosis, who are in remission (complete or partial) following platinum-based chemotherapy; maintenance therapy

• Overall, the G-BA concludes that the additional benefit of niraparib compared with olaparib is not proven.
• mortality
  • Overall survival was defined in the NOVA, SOLO2 and Study 19 trials as the period from randomisation to death from any cause.
  • For the endpoint of overall survival, the adjusted indirect comparison showed no statistically significant difference between niraparib and olaparib (HR: 0.99 [95% CI: 0.61; 1.60]; p=0.956).
  • No additional benefit was identified for the endpoint of overall survival.
• morbidity
  • As no results regarding progression-free survival were reported for the overall study populations, no usable data are available for this endpoint.
  • Against this background, there are major differences in the follow-up strategy between the two studies with regard to the health status endpoint. The analyses between the NOVA and SOLO2 studies are therefore not comparable and cannot be used for an indirect comparison. Consequently, no usable data are available for the health status endpoint.
  • Consequently, no usable data are available regarding symptoms.
• Health-related quality of life
  • There is therefore insufficient data available for an indirect comparison. Consequently, no usable data on health-related quality of life is available.
• Side effects
  • In the NOVA study, it was planned to record adverse events (AEs) and severe AEs (CTCAE grade ≥ 3) up to the last dose of the study medication.
  • In the NOVA study, on the niraparib side of the indirect comparison, an adverse event occurred in 100% of patients in the intervention arm, compared with 95.5% of patients in the comparator arm.
  • The results for the SAE endpoint indicate no statistically significant difference between niraparib and olaparib (HR: 1.14 [95% CI: 0.57; 2.30]). However, as explained above, the certainty of the results is insufficient for this set of data to allow a reliable interpretation of this finding.
  • In the adjusted indirect comparison, a statistically significant effect with a disadvantage for niraparib compared with olaparib was observed for the endpoint of severe AEs.
  • The results for the endpoint ‘discontinuation due to AEs’ indicate no statistically significant difference between niraparib and olaparib (HR: 2.15 [95% CI: 0.46; 9.97]). However, as explained above, the certainty of the results for this endpoint is also insufficient for a reliable interpretation of this finding given the nature of the data.
  • No usable data are available for the specific AEs, particularly due to the lack of analyses for the overall population of the NOVA study.
• Overall assessment
  • For the assessment of the additional benefit of niraparib compared with olaparib, an adjusted indirect comparison of niraparib (NOVA study) with olaparib (SOLO2 study and Study 19) via the bridge comparator placebo is available.
  • In the mortality endpoint category, the indirect comparison for the overall survival endpoint shows no statistically significant difference between niraparib and olaparib. In this regard, only a minor number of events had occurred in the niraparib group (NOVA study) at the time of the current data cut-off. Final analyses from the NOVA study on the endpoint of overall survival are pending. No additional benefit was identified for the endpoint of overall survival.
  • No usable data were available for the endpoint categories of morbidity and health-related quality of life.
  • In the side effects category, an indirect comparison for the endpoint of severe AEs (CTCAE grade ≥ 3) showed a disadvantage for niraparib compared with olaparib. The results for the endpoints of SAEs and discontinuation due to AEs showed no statistically significant difference between niraparib and olaparib; however, there was insufficient certainty regarding these results. No usable data were available for specific AEs.
  • With regard to overall survival, however, no difference was observed between niraparib and olaparib in the NOVA trial, although the number of events was still minor.
  • Taking clinical relevance into account, the disadvantage in terms of side effects – given that moderate disadvantages were observed only for the endpoint of severe AEs (CTCAE grade ≥ 3), the extent of these disadvantages does not, in the current data set, reach a level that would justify less benefit in the overall assessment.
  • Overall, the G-BA concludes that the additional benefit of niraparib over olaparib is not proven.

Courtesy translation only, please refer to the German original.