Niraparib (4) – 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 trial is a multicentre, double-blind, randomised, controlled trial comparing olaparib with placebo.

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

• For the treatment of adult female patients with recurrent platinum-sensitive, high-grade serous carcinoma of the ovary, fallopian tubes or primary peritoneal carcinoma who are in remission (complete or partial) following platinum-based chemotherapy; the additional benefit is not proven.
• mortality
  • For the endpoint of overall survival, no statistically significant difference was observed between niraparib and olaparib in the adjusted indirect comparison.
  • No additional benefit is identified for the endpoint of overall survival.
• morbidity
  • No usable data are available for the adjusted indirect comparison regarding progression-free survival.
  • No usable data are available for the health status endpoint, as measured by the VAS of the EQ-5D, as different follow-up strategies were used for this endpoint in the studies.
  • Consequently, no usable data are available regarding symptoms.
• quality of life
  • To assess health-related quality of life, the total score of the disease-specific FACT-O questionnaire was collected in the SOLO2 and Study 19 trials, but not in the NOVA trial. Consequently, there are insufficient data available for an indirect comparison.
  • Consequently, there are no usable data on health-related quality of life.
• Side effects
  • Adverse events occurred at least once in almost all patients in the treatment groups of the studies. The results are therefore presented for supplementary information only.
  • For the SUEs endpoint, the results on the niraparib side of the indirect comparison are potentially highly biased. Consequently, the criteria for deriving reliable conclusions from an adjusted indirect comparison are not met here either.
  • On the niraparib side of the adjusted indirect comparison, only the results from the NOVA study – which have a high potential for bias with regard to the endpoint – are available. The criteria for deriving conclusions on additional benefit from an adjusted indirect comparison are therefore not met in principle at this stage. However, in the adjusted indirect comparison with olaparib, a large, statistically significant disadvantage compared to niraparib is evident.
  • For the endpoint ‘discontinuation due to AEs’, only results with limited certainty of outcome are available on the niraparib side of the indirect comparison. Consequently, the prerequisites for drawing conclusions regarding additional benefit from an adjusted indirect comparison are not met here either.
  • No usable data are available for the specific AEs of particular significance, as different follow-up strategies were applied for these endpoints in the studies. For the specific AE of pneumonitis, there are too few events to calculate an adjusted indirect comparison.
  • In the overall assessment of the results on side effects, the adjusted indirect comparison provides analyses only for serious AE events that allow for conclusions with sufficient certainty. Consequently, no conclusions can be drawn regarding serious AE events, specific AE events or discontinuations due to AE events.
• Overall assessment / Conclusion
  • An adjusted indirect comparison of niraparib (NOVA trial) with olaparib (SOLO2 trial and Trial 19), using placebo as the bridge comparator, is available for the assessment of the additional benefit of niraparib.
  • For the endpoint of overall survival, the adjusted indirect comparison shows no statistically significant difference between niraparib and olaparib. No additional benefit is therefore identified for the endpoint of overall survival.
  • No usable data are available for the endpoint categories of morbidity and health-related quality of life.
  • In the side effects endpoint category, no usable data are available for the endpoints of SAEs, discontinuation due to AEs, or specific AEs.
  • Based on the adjusted indirect comparison for the endpoint ‘severe AEs’ (CTCAE grade ≥ 3), there is a statistically significant disadvantage for niraparib compared with olaparib. However, it cannot be assumed that this large effect as a disadvantage for niraparib can be entirely called into question by potential biases.
  • Overall, results from the adjusted indirect comparison are available only for the endpoint categories of mortality and side effects.
  • These show exclusively a disadvantage for treatment with niraparib compared with olaparib.
  • Whilst the negative effect of niraparib compared with olaparib in terms of severe adverse events cannot be entirely called into question by potential biases, its significance, extent and therapeutic significance—taking into account the lack of usable data for other endpoints in the ‘side effects’ category, as well as the statements from medical societies—are not considered sufficient to conclude, in the overall assessment, that niraparib offers less benefit than olaparib. It is therefore concluded that the additional benefit of niraparib over olaparib is not proven.

Courtesy translation only, please refer to the German original.