A targeted therapy already used to treat advanced skin cancer is also effective against the most common subtype of medulloblastoma in adults and should be considered for treatment in patients with new diagnoses, according to research published in the Journal of Clinical Oncology (2015; doi:10.1200/JCO.2014.60.1591).

The drug, vismodegib, is designed to block a key protein in the sonic hedgehog (SHH) signaling pathway. The pathway is normally active during fetal development and is inappropriately switched on in approximately 30% of medulloblastoma tumors, including approximately 60% of tumors in adults and 25% of tumors in children.

Medulloblastoma develops in the cerebellum at the base of the skull and involves four different subtypes, each with different genetic alterations. The tumor is diagnosed in as many as 400 children and adolescents annually in the United States, making it the most common malignant pediatric brain tumor. Medulloblastoma is less common in adults, who account for approximately one-third of new cases each year.

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As expected, only patients with the SHH subtype responded to vismodegib; however, researchers also reported that the drug was not universally effective against all tumors in the subtype. The research was led by St. Jude Children’s Research Hospital in Memphis, Tennessee.

“While it was disappointing that not all medulloblastoma patients with the SHH subtype will benefit, for the right patients these results mark the beginning of a new era of targeted therapy for treatment of this tumor,” said first and corresponding author Giles Robinson, MD, an assistant member of the St. Jude Department of Oncology.

“The findings also highlight the importance of ongoing research to identify the genetic alterations that define who the right patients are and help identify those most likely to benefit from this drug as well as those for whom different therapy is needed.”

Vismodegib received FDA approval in 2012 for treatment of adults with advanced basal cell carcinoma. Preclinical research by St. Jude scientists helped to set the stage for trials of the drug in patients with medulloblastoma.

This Pediatric Brain Tumor Consortium study involved Phase II clinical trials that included 31 adults and 12 children with advanced medulloblastoma. Participants all had medulloblastoma that persisted or returned following standard treatment with surgery, radiation, and combination chemotherapy.

Tumors shrank or disappeared completely for 8 weeks or more in four study participants, including three adults, following treatment with vismodegib. In 13 patients (41% of participants with SHH medulloblastoma), the disease stabilized and tumors stopped growing for as long as 17 months during vismodegib therapy.

The findings led to the drug being included in the St. Jude clinical trial for newly diagnosed pediatric medulloblastoma in patients ages 3 to 22 years. Patients with SHH medulloblastoma receive vismodegib as maintenance therapy.

“Tumor response to vismodegib in this study was transient, probably due to the development of drug resistance,” Robinson said. “The finding that these tumors also contain other targetable mutations suggests several possible combination therapies that may increase sensitivity to vismodegib and combat drug resistance.”