# Vismodegib in recurrent sonic hedgehog-subgroup medulloblastoma (PBTC-025B and PBTC-032)

Source: https://onco.cc/key-papers/paper-robinson-vismodegib-shh-medulloblastoma-jco-2015/  
OnCo record `paper-robinson-vismodegib-shh-medulloblastoma-jco-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: Journal of Clinical Oncology
- Year: 2015
- DOI: 10.1200/JCO.2014.60.1591
- Authors: Robinson GW, Orr BA, Wu G, et al.
- Findings: Responses only in SHH-subgroup tumours with upstream (PTCH1, SMO) alterations.; No responses in non-SHH medulloblastoma.
- What it means: Vismodegib or sonidegib is reserved for skeletally mature patients with relapsed SHH medulloblastoma and upstream pathway mutations, a niche defined by this trial.
- Caveats: Small numbers; responses were transient.; Irreversible growth plate closure in growing children.

## Sources

- J Clin Oncol 2015: https://doi.org/10.1200/JCO.2014.60.1591
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26169613/

## Connected records

- cancers: [SHH-activated medulloblastoma](https://onco.cc/cancers/medulloblastoma-shh/)
- drugs: [Vismodegib](https://onco.cc/drugs/vismodegib/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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