Selinexor (1) – Nexpovio®

• Clinical trials
  • The benefit assessment is based on the results of the randomised, open-label, actively controlled Phase III BOSTON trial. The trial compares selinexor in combination with bortezomib and dexamethasone against bortezomib and dexamethasone alone.

Adults with multiple myeloma who have received at least one prior course of treatment

• Overall, additional benefit is not proven for selinexor in combination with bortezomib and dexamethasone in adults with multiple myeloma who have received at least one prior line of treatment.
• mortality
  • For the endpoint of overall survival, there is no statistically significant difference between selinexor in combination with bortezomib and dexamethasone and bortezomib in combination with dexamethasone.
  • The result for this endpoint is to be regarded as majorly biased for the reasons stated above.
• Morbidity – Progression-free survival
  • PFS is statistically significantly prolonged with selinexor in combination with bortezomib and dexamethasone compared with bortezomib in combination with dexamethasone.
  • The results for the progression-free survival endpoint are therefore not taken into account in this assessment.
• Morbidity – Symptoms
  • The results presented for the endpoints ‘symptoms’ assessed using the EORTC QLQ-C30 and ‘symptoms’ assessed using the EORTC QLQ-CIPN20 are therefore not evaluable.
• Morbidity – Health status
  • Taking into account the comments in the ‘Symptoms’ section regarding the different assessment time points in the two study arms, the results for the health status endpoint are not suitable for this benefit assessment.
• morbidity
  • In the overall assessment of the morbidity endpoint category, no suitable data are available.
• quality of life
  • Taking into account the comments in the ‘Symptoms’ section regarding the different assessment time points in the two study arms, the results on health-related quality of life are not suitable for the present benefit assessment.
  • In the overall assessment of the health-related quality of life endpoint category, there are therefore no evaluable data available.
• Side effects – serious AEs (SAEs) and severe AEs (CTCAE grade ≥ 3)
  • For the endpoints SAE and severe AEs (CTCAE grade ≥ 3), a statistically significant difference was observed between the treatment arms, with a disadvantage for selinexor in combination with bortezomib and dexamethasone.
• Side effects – therapy discontinuations due to AEs
  • For the endpoint of therapy discontinuations due to AEs, there was no statistically significant difference between the treatment groups.
• Side effects – Specific AEs
  • For the specific AEs involving gastrointestinal disorders (severe AEs) and cataracts (severe AEs), a statistically significant difference was observed between the treatment arms, with a disadvantage for selinexor in combination with bortezomib and dexamethasone.
  • For the endpoints of cardiac disorders (adverse events), disorders of the respiratory tract, thoracic cavity and mediastinum (severe adverse events), disorders of the blood and lymphatic system (severe adverse events), general disorders and administration site conditions (severe AEs) and metabolic and nutritional disorders (severe AEs), a statistically significant difference was observed in each case to the disadvantage of selinexor + bortezomib + dexamethasone compared with bortezomib + dexamethasone.
  • The results for the specific AE ‘peripheral neuropathies’ are therefore considered to be uninterpretable.
• Side effects
  • In the overall analysis of the ‘side effects’ endpoint category, disadvantages were observed for the endpoints SAE, severe AEs (CTCAE grade ≥ 3) and specific AEs for selinexor in combination with bortezomib and dexamethasone compared with bortezomib and dexamethasone. These disadvantages are considered to be clinically significant for patients.
• Overall assessment / Conclusion
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment arms. The result for this endpoint is considered to be majorly biased.
  • This is due in particular to a high proportion of patients in the control arm of the study who switched to a selinexor-containing regimen at an early stage. Furthermore, there are doubts as to the extent to which the bortezomib-containing treatment regimen used was appropriate in the present treatment setting, in which a significant proportion of patients had already received prior bortezomib therapy.
  • No suitable data are available for an overall assessment of the morbidity results. The data on patient-reported endpoints in the categories of morbidity and health-related quality of life cannot be evaluated due to widely varying assessment time points and a major difference in the number of assessments between the two study arms.
  • In the side effect category, statistically significant differences were observed in the endpoints of SAE and severe AEs (CTCAE grade ≥ 3), as well as in specific AEs, between the treatment arms to the disadvantage of the intervention. By contrast, there were no differences between the treatment arms in terms of therapy discontinuations due to AEs.
  • When all results are considered as a whole, the only disadvantages for selinexor in combination with bortezomib and dexamethasone compared with bortezomib in combination with dexamethasone are the increased incidence of side effects.
  • However, taking clinical relevance into account, the extent of these disadvantages is not such that it would justify less benefit in the overall assessment of all endpoints.
  • Overall, additional benefit is not proven for selinexor in combination with bortezomib and dexamethasone in adults with multiple myeloma who have received at least one prior line of treatment.

Courtesy translation only, please refer to the German original.