Netupitant / Palonosetron (1) – Akynzeo®

• Clinical trials
  • The NETU-08-18 trial is a randomised, actively controlled, double-blind trial sponsored by the pharmaceutical manufacturer.
  • The NETU-10-29 trial is a randomised, actively controlled, double-blind trial sponsored by the pharmaceutical manufacturer, which was conducted at 59 centres worldwide.

a) Prevention of acute and delayed nausea and vomiting associated with moderately emetogenic chemotherapy for cancer

• The additional benefit is not proven.
• Consequently, no relevant data were available for the assessment of the additional benefit of netupitant/palonosetron in the prevention of acute and delayed nausea and vomiting associated with moderately emetogenic chemotherapy. There is therefore no hint of any additional benefit of netupitant/palonosetron compared with the appropriate comparator therapy.

b) Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based chemotherapy for cancer

• An additional benefit is not proven.
• Overall, additional benefit from netupitant/palonosetron compared with the appropriate comparator therapy is not proven for adult patients receiving highly emetogenic cisplatin-based chemotherapy for the prevention and treatment of nausea and vomiting.
• mortality
  • For the endpoint of overall mortality, the NETU-10-29 study showed no statistically significant difference between the treatment groups. There is no hint of additional benefit from netupitant/palonosetron compared with aprepitant + palonosetron + dexamethasone.
• Morbidity – Nausea
  • No usable data were available in the dossier for the endpoint of nausea. Assessment using a visual analogue scale (VAS) is generally appropriate. However, it is unclear on what basis the cut-off value of 25 mm was chosen for the operationalisation of ‘major nausea’; no literature on validation was provided.
  • With regard to the analyses of the maximum intensity of nausea submitted subsequently during the commenting procedure, the pharmaceutical manufacturer merely assumes that netupitant/palonosetron is non-inferior. Overall, there is no hint of an additional benefit of netupitant/palonosetron compared with aprepitant + palonosetron + dexamethasone.
• Morbidity – Vomiting
  • For the endpoint of vomiting, results were available only for the first cycle of chemotherapy. As patients in the study received a variable number of chemotherapy cycles, it is particularly relevant for the benefit assessment whether an antiemetic effect persists over several cycles of chemotherapy. Consideration of results for the first cycle of chemotherapy alone is regarded as too uncertain and therefore insufficient for the assessment of additional benefit.
  • Although a statistically significant difference in favour of netupitant/palonosetron in combination with dexamethasone was observed for the first cycle of chemotherapy, an analysis covering the entire study duration was not provided. Consequently, the data presented for this endpoint are insufficient to establish additional benefit.
• Health-related quality of life
  • Health-related quality of life was not investigated in the NETU-10-29 study. There is no hint of additional benefit from netupitant/palonosetron compared with aprepitant + palonosetron + dexamethasone; additional benefit is therefore not proven.
• Side effects – serious adverse events
  • For the endpoint of serious adverse events, the NETU-10-29 study showed no statistically significant difference between the treatment groups. There is no hint that netupitant/palonosetron causes greater or minor harm compared with aprepitant + palonosetron + dexamethasone; greater or minor harm is therefore not proven.
• Side effects – discontinuation due to adverse events
  • For the endpoint of discontinuation due to adverse events, the NETU-10-29 study showed no statistically significant difference between the treatment groups. There is no hint that netupitant/palonosetron causes greater or lesser harm compared with aprepitant + palonosetron + dexamethasone; therefore, it is not proven that it causes greater or minor harm.
• Side effects – diarrhoea
  • For the endpoint of diarrhoea, a statistically significant difference was observed in favour of netupitant/palonosetron. The chemotherapy regimens in the two treatment arms did not differ substantially; it is therefore unlikely that the observed effect is attributable to the chemotherapy regimens.
  • To infer an additional benefit based solely on the avoidance of side effects, evidence of non-inferiority in terms of efficacy would be required; however, as outlined, there are insufficient data available for this. Against this background, the positive result in the area of side effects cannot be taken into account when determining additional benefit.

Courtesy translation only, please refer to the German original.