Vemurafenib Monotherapy Not Active in BRAF V600E Colorectal Cancer

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Single-agent vemurafenib did not show meaningful clinical activity in patients with BRAF V600E-mutant colorectal cancer.
Single-agent vemurafenib did not show meaningful clinical activity in patients with BRAF V600E-mutant colorectal cancer.

Although vemurafenib monotherapy is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with BRAF V600-mutant unresectable or metastatic melanoma, single-agent vemurafenib did not show meaningful clinical activity in patients with BRAF V600E-mutant colorectal cancer (CRC), a new study published online ahead of print in the Journal of Clinical Oncology has shown.1

Because the BRAF V600E is seen in 5% to 8% of patients with metastatic CRC and is associated with poor prognosis, researchers sought to evaluate vemurafenib, an oral BRAF V600 kinase inhibitor with pronounced activity in patients with metastatic melanoma, in patients with BRAF V600E-positive metastatic CRC.

For the multicenter, open-label study, researchers enrolled 21 patients with metastatic CRC with BRAF V600 mutations. Of those, 20 had received at least 1 prior metastatic chemotherapy regimen. All patients received vemurafenib 960 mg orally twice daily.

Results showed that of the 21 patients treated, 1 patient had a confirmed partial response (5%; 95% CI: 1 – 24) and 7 others had stable disease. Researchers found that median progression-free survival was 2.1 months.

In regard to safety, grade 3 toxicities included arthralgia, fatigue, keratoacanthomas, and rash.

RELATED: Extended RAS Mutation Testing in Colorectal Cancer Predicts EGFR MoAb Response

The study also demonstrated concurrent KRAS and NRAS mutations in a subset of patients' tumors, which was the cause of acquired resistance in vemurafenib-sensitive patient models.

“Combination strategies are now under development and may be informed by the presence of intratumor heterogeneity of KRAS and NRAS mutations,” the authors concluded.

Reference

  1. Kopetz S, Desai J, Chan E, et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer [published online ahead of print on October 12, 2015]. J Clin Oncol. doi: 10.1200/JCO.2015.63.2497.

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