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EORTC-NCI-AACR: Dabrafenib Plus Trametinib Active in Some BRAF V600E–Mutated Gastrointestinal Cancers

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Key Points

  • Investigator-assessed overall response rate to the combination was 41% (13 of 32) in patients with biliary tract cancer and 67% (2 of 3) in patients with adenocarcinoma of the small intestine.
  • The median time [to progression] was 7.2 months, with some patients surviving without their disease progressing for more than 1 year.
  • The median overall survival time was 11.3 months, with some surviving up to 2 years.
 

In a late-breaking presentation at the 30th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Zev Wainberg, MD, reported on results from a phase II international clinical trial of dabrafenib (Tafinlar) plus trametinib (Mekinist), which showed some activity in 36 patients with biliary tract cancer and adenocarcinoma of the small intestine (Abstract 2LBA). Patients in the trial had mutations in the BRAF V600E gene, which is implicated in about 15% of biliary tract cancers and adenocarcinomas of the small intestine. 

Both dabrafenib and trametinib were given orally: 150 mg of dabrafenib twice a day and 2 mg of trametinib once a day.

Trial Results

The investigator-assessed overall response rate to the combination of dabrafenib plus trametinib was 41% (13 of 32) in patients with biliary tract cancer and 67% (2 of 3) in patients with adenocarcinoma of the small intestine.

Dr. Wainberg, Associate Professor of Medicine at the University of California, Los Angeles, said in a statement, “As of the end of October [2018], 6 of the [patients with] biliary tract cancers were still responding to the treatment, and responses had lasted for at least 6 months in 7 patients. The median time [to progression] was 7.2 months, with some patients surviving without their disease progressing for more than 1 year. The median overall survival time was 11.3 months, with some surviving up to 2 years.”

He added: “These are patients with rare, aggressive cancers that have very poor prognoses and for whom there are currently limited therapeutic options. Their cancer has failed to respond to previous treatments—at least 2 prior chemotherapies had failed in 78% of them—so these are significant and promising results that provide proof that BRAF is a validated target in patients with biliary tract cancer… The results support the idea that all biliary tract cancer patients should be tested to see if they have the mutation.”

Grade 3/4 adverse events included increased γ-glutamyltransferase (in 3 patients with biliary tract cancer [9%]), decreased white blood cell count (in 3 patients with biliary tract cancer [9%]), and pyrexia (in 2 patients with biliary tract cancer [6%] and in 1 patient [33%] with adenocarcinoma of the small intestine).

Dr. Wainberg concluded, “There is an urgent unmet need for these patients, and we believe these exciting data represent a potential new treatment option for patients with this BRAF mutation.”

Disclosure: See study authors’ full disclosures at ecco-org.eu.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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