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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial

Vivek Subbiah1, Robert J Kreitman2, Zev A Wainberg3

  • 1Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. vsubbiah@mdanderson.org.

Nature Medicine
|April 14, 2023
PubMed

Insights

Dabrafenib plus trametinib showed significant efficacy in BRAFV600E-mutated rare cancers. This combination therapy offers a promising treatment for patients with these challenging advanced malignancies.

Area of Science:

  • Oncology
  • Medical Genetics
  • Pharmacology

Background:

  • BRAFV600E mutations are key drivers in various rare cancers.
  • Targeted therapies are crucial for improving outcomes in these difficult-to-treat malignancies.

Purpose of the Study:

  • To evaluate the efficacy and safety of dabrafenib plus trametinib in patients with BRAFV600E-mutated advanced rare cancers.
  • To assess overall response rate, duration of response, progression-free survival, and overall survival across eight distinct cancer cohorts.

Main Methods:

  • Phase 2 basket trial enrolling patients with BRAFV600E-mutated anaplastic thyroid carcinoma, biliary tract cancer, gastrointestinal stromal tumor, adenocarcinoma of the small intestine, low-grade glioma, high-grade glioma, hairy cell leukemia, and multiple myeloma.
  • Investigator-assessed overall response rate (ORR) as the primary endpoint.
  • Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety analysis.

Main Results:

  • The overall response rate (ORR) varied across cohorts, with notable responses in hairy cell leukemia (89%), adenocarcinoma of the small intestine (67%), and anaplastic thyroid carcinoma (56%).
  • Median duration of response (DoR) and overall survival (OS) were encouraging in several cohorts, with some reaching not estimable.
  • Common treatment-related adverse events included pyrexia, fatigue, chills, nausea, and rash, generally manageable.

Conclusions:

  • Dabrafenib plus trametinib demonstrated significant tumor-agnostic activity in BRAFV600E-mutated advanced rare cancers.
  • This combination therapy represents a promising treatment strategy for select patients with these rare oncological conditions.
  • Further investigation is warranted to optimize treatment paradigms for BRAFV600E-mutated rare cancers.

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