Vandetanib (3) – Caprelsa®

Paediatric population (adolescents and children aged 5 years and over with aggressive and symptomatic medullary thyroid carcinoma (MTC) in cases of unresectable, locally advanced or metastatic disease)

• For vandetanib for the treatment of adolescents and children aged 5 years and older with aggressive and symptomatic medullary thyroid carcinoma (MTC) in patients with unresectable, locally advanced or metastatic disease, based on the extrapolation of evidence to a paediatric population, there is a hint of an additional benefit compared with the appropriate comparator therapy; however, this additional benefit is non-quantifiable because the current scientific data do not permit this.
• On the basis of the criteria set out in Section 5(7) of the AM-NutzenV, the G-BA classifies the extent of the additional benefit as non-quantifiable.
• Taking into account the lack of alternative treatments for children and adolescents, the severity and rarity of the condition, and the therapeutic aim of the treatment, there is, despite the clear limitations of the available evidence, a hint of a non-quantifiable additional benefit for the endpoint ‘time to pain progression’ compared with the appropriate comparator therapy, best supportive care; however, this is non-quantifiable because the scientific evidence does not permit it.
• mortality
  • In the paediatric study 98, one death occurred in the vandetanib group up to the data cut-off date of 17 July 2011.
• Morbidity – Progression-free survival
  • The median progression-free survival was 46 months.
• Morbidity – Time to pain progression
  • Given the known pathology of the disease and taking into account the current state of medical knowledge regarding the treatment of children and adolescents, it is therefore reasonable to assume that children and adolescents at this stage of the disease will experience pain. Against this background, and in view of the results regarding the efficacy and safety of the paediatric study – which show effects largely consistent with those of the adult study – and given the identical appropriate comparator therapies for both populations, it is assumed that the established additional benefit of the endpoint ‘time to pain progression’ is transferable from the adult population to the paediatric population; however, due to the uncertainties described, the extent of this benefit is non-quantifiable.
• Side effects
  • Adverse events occurred in all patients; one patient (6.3%) experienced a severe adverse event, and severe adverse events (CTCAE grade ≥ 3) occurred in 13 patients (81.3%).
  • The most common adverse events and adverse events of special interest included diarrhoea, QTc prolongation and rash (acne, acne-like), which occurred in 15 patients (93.8%), 2 patients (12.5%) and 13 patients (81.3%), respectively.
  • No patient discontinued treatment with vandetanib due to adverse events.
  • In this regard, the EMA notes that diarrhoea and QTc prolongation also occurred frequently in the adult population, although the incidence rates were lower than in children. The most common severe adverse events (CTCAE ≥ 3) included, amongst others, diarrhoea, which was also one of the most common CTCAE ≥ 3 events in the adult study.
• Conclusion
  • Based on the extrapolation of evidence from the adult study to the paediatric population, the G-BA recognises an additional benefit of vandetanib for adolescents and children aged 5 years and older for the treatment of aggressive and symptomatic medullary thyroid carcinoma (MTC) in patients with unresectable, locally advanced or metastatic disease.

Courtesy translation only, please refer to the German original.