Vismodegib in recurrent sonic hedgehog-subgroup medulloblastoma (PBTC-025B and PBTC-032)
The hedgehog pathway inhibitor vismodegib produced responses in recurrent SHH-subgroup medulloblastoma but not in other subgroups, and only in tumours whose mutation lay upstream of the drug's target, showing that molecular subgrouping must guide its use.
Overview
Two phase 2 studies of vismodegib in 43 patients (adults and children) with recurrent medulloblastoma, analysed by molecular subgroup and mutation.
Responses occurred in 3 of 12 adults and 1 of 8 children with SHH-subgroup tumours and in none of the 20 non-SHH patients; responders had PTCH1 or SMO alterations, while tumours with downstream SUFU or GLI2 alterations did not respond, and growth plate fusion occurred in children.
- Responses only in SHH-subgroup tumours with upstream (PTCH1, SMO) alterations.
- No responses in non-SHH medulloblastoma.
Vismodegib or sonidegib is reserved for skeletally mature patients with relapsed SHH medulloblastoma and upstream pathway mutations, a niche defined by this trial.
- Small numbers; responses were transient.
- Irreversible growth plate closure in growing children.
Similar pages
not linked directly; found by shared links- Key paperSubgroup-specific prognostic implications of TP53 mutation in medulloblastoma
Shares SHH-activated medulloblastoma, Journal of Clinical Oncology.
- TermMedulloblastoma molecular groups (WNT, SHH, group 3, group 4)
Shares Vismodegib, SHH-activated medulloblastoma.
- TargetSmoothened (hedgehog pathway)
Shares Vismodegib, SHH-activated medulloblastoma.