Selpercatinib (8) – Retsevmo®

• Clinical trials
  • The LIBRETTO-531 trial is an ongoing, multicentre, open-label, randomised controlled Phase III trial comparing selpercatinib with cabozantinib or vandetanib, each used as monotherapy.

Adults and adolescents aged 12 years and over with advanced medullary thyroid carcinoma harbouring a RET (rearranged during transfection) receptor tyrosine kinase mutation; first-line treatment

• Consequently, selpercatinib is found to offer major additional benefit over cabozantinib or vandetanib for the first-line treatment of advanced RET-mutated MTC in adults and adolescents aged 12 years and over.
• In summary, the G-BA therefore derives an indication for the established additional benefit with regard to the certainty of the finding (probability of additional benefit).
• mortality
  • For the endpoint of overall survival, there is a statistically significant advantage in favour of selpercatinib compared with cabozantinib or vandetanib.
  • The extent of the prolongation achieved in overall survival is assessed as a very marked improvement.
• Morbidity – Progression-free survival (PFS)
  • In the LIBRETTO-531 trial, PFS was defined as the time from randomisation to the first documented occurrence of disease progression or death from any cause, whichever occurred first.
  • There is a statistically significant advantage for selpercatinib compared with the control arm.
• Morbidity – Symptoms (assessed using the EORTC QLQ-C30 and Worst Pain NRS)
  • The pharmaceutical manufacturer submitted analyses for the benefit assessment covering the time to the first deterioration of at least 10 points on the EORTC QLQ-C30 and at least 2 points on the Worst Pain NRS.
  • In the EORTC QLQ-C30, a statistically significant advantage in favour of selpercatinib compared with cabozantinib or vandetanib was observed for the endpoints of fatigue, nausea and vomiting, pain, insomnia, loss of appetite and diarrhoea.
  • By contrast, no significant differences were observed between the treatment arms for the dyspnoea and constipation symptom scales of the EORTC QLQ-C30.
  • For the ‘Worst Pain NRS’ pain scale, a statistically significant advantage was observed in favour of selpercatinib compared with the control arm for the endpoint of pain.
• Morbidity – Health status (assessed using the EQ-5D VAS)
  • Health status is assessed using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • A statistically significant advantage was observed for the health status endpoint, favouring selpercatinib compared with cabozantinib or vandetanib.
• Quality of life – EORTC QLQ-C30
  • In the LIBRETTO-531 study, patients’ quality of life is assessed using the functional scales of the EORTC QLQ-C30 questionnaire.
  • For all scales of the EORTC QLQ-C30 (overall health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning), a statistically significant advantage was observed in favour of selpercatinib compared with cabozantinib or vandetanib.
• Side effects – serious AEs (SAEs), severe AEs (CTCAE grade ≥ 3), therapy discontinuation due to AEs
  • For the endpoints SAE, severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs, selpercatinib showed statistically significant advantages compared with cabozantinib or vandetanib.
• Side effects – Specific AEs
  • In detail, statistically significant advantages in favour of selpercatinib were observed for specific adverse events with regard to the endpoints gastrointestinal disorders (SOC, AEs), diarrhoea (PT, AEs), nausea (PT, AEs), vomiting (PT, AEs), asthenia (PT, AEs), skin and subcutaneous tissue disorders (SOC, AEs), metabolic and nutritional disorders (SOC, severe AEs), nervous system disorders (SOC, severe AEs), blood and lymphatic system disorders (SOC, severe AEs), stomatitis (PT, AEs), mucositis (PT, AEs), palmar-plantar erythrodysesthesia syndrome (PT, AEs) and disorders of the respiratory tract, thoracic cavity and mediastinum (SOC, severe AEs).
  • For the endpoints dry mouth (PT, AEs) and elevated alanine aminotransferase (PT, severe AEs), a statistically significant difference was observed in each case to the disadvantage of selpercatinib.
• Overall assessment
  • Results for the additional benefit of Selpercatinib for the first-line treatment of advanced RET-mutated MTC in adults and-531 are available for comparison with cabozantinib or vandetanib across the endpoint categories of mortality, morbidity, quality of life and side effects.
  • For overall survival, there is a statistically significant advantage in favour of selpercatinib compared with cabozantinib or vandetanib. The prolongation in overall survival achieved is assessed as a very marked improvement.
  • With regard to quality of life, selpercatinib shows exclusively advantages compared with the appropriate comparator therapy.
  • In the morbidity endpoint category, selpercatinib also demonstrated advantages over the appropriate comparator therapy in terms of disease symptoms and health status (assessed using the EORTC QLQ-C30, Worst Pain NRS and EQ-5D-VAS).
  • For the endpoint category of side effects, selpercatinib shows exclusively advantages in the results for severe SAEs, severe adverse reactions (SARs) and therapy discontinuation due to AEs. In detail, there are also predominantly advantages with regard to specific AEs.
  • In the overall assessment of the available results for patient-relevant endpoints, selpercatinib is found to offer a significant improvement in treatment-related benefit—unprecedented to date—across all endpoint categories and, in particular, in terms of overall survival, compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.