Beyond Skin Cancer: BRAF Inhibition in Solid Tumors Including Colorectal Cancer
Posted: Thursday, June 11, 2020
In cancers with BRAF V600 mutations, single-agent treatment BRAF inhibition with vemurafenib may prove to have broader clinical activity than was previously recognized, with responses reported in 13 different types of cancer. Vivek Subbiah, MD, of The University of Texas MD Anderson Cancer Center, and colleagues published their findings in Cancer Discovery.
“BRAF V600 mutations lead to oncogene addiction and are clinically actionable in a broad range of non-melanoma cancers, including tumor types in which RAF inhibition is not currently considered standard of care,” concluded the authors.
This basket study in BRAF V600 mutation–positive solid tumors included 172 patients with measurable disease that was refractory to standard therapy. Patients had a range of cancer diagnoses, such as colorectal cancer, non–small cell lung cancer, glioma, histiocytosis, and salivary duct cancer. Response to therapy was assessed using imaging of the chest, abdomen, and pelvis every 8 weeks.
After a median follow-up of 10.7 months, the objective response rate was 32.6%, with complete responses in 3% of patients, partial responses in 30% of patients, and stable disease in 38% of patients. These responses were observed across the 13 unique cancer types represented in the study, including 6 patients with colorectal cancer. The median duration of response was 13.1 months, and the median progression-free survival was 5.8 months. The clinical benefit rate, defined as partial response of any duration or stable disease for more than 6 months, was 42%.
The most common reason for discontinuation of vemurafenib was progressive disease (61%), adverse events (12%), and patient withdrawal (8%). Adverse events occurred in more than 20% of patients, with the most common being arthralgia, fatigue, and hyperkeratosis. Grade 3 or higher adverse events occurred in 76% of patients, most commonly squamous cell carcinoma of the skin, keratoacanthoma, and maculopapular rash.
Disclosure: For the full list of authors’ disclosures, visit cancerdiscovery.aacrjournals.org.