Vemurafenib Active in Melanoma With Brain Metastases

Patients with metastatic melanoma and brain metastases achieved clinically meaningful response rates with vemurafenib without experiencing significant central nervous system toxicity, according to a study published in the Annals of Oncology.¹

Vemurafenib is a kinase inhibitor indicated for the treatment of patients with BRAF V600E mutation-positive unresectable or metastatic melanoma. Researchers evaluated the overall response rate of vemurafenib among patients with brain metastases, previously treated or untreated.

For the international, phase 2 study, investigators enrolled 146 patients with BRAF V600-mutant melanoma. Of those, 90 with previously untreated brain metastases were assigned to cohort 1 and 56 with previously treated brain metastases were assigned to cohort 2. All participants received vemurafenib 960 mg orally twice daily until disease progression or unacceptable toxicity.

The intracranial best overall response rate in cohort 1 was 18%, including 2 complete and 14 partial responses. The extracranial best overall response rate was 33% in cohort 1 and 23% in cohort 2.

Median intracranial duration of response was 4.6 months in cohort 1 and 6.6 months in cohort 2 per independent review committee. Median extracranial duration of response was 7.7 months and 11.1 months for cohort 1 and cohort 2, respectively.

The median progression-free survival was 3.7 months in cohort 1 and 4.0 months in cohort 2; the median overall survival rates were 8.9 months and 9.6 months, respectively.

The incidence of toxicities was similar between the 2 cohorts with respect to type, grade, and frequency. Sixty-six percent of patients in cohort 1 had grade 3 to 4 adverse events vs 64% of those in cohort 2. Two patients died from adverse events cohort 1; 1 patient died from adverse events cohort 2.

Although these findings show clinically meaningful response rates in this population with poor prognosis, larger studies are needed to validate these results and to assess BRAF pathway inhibition in combination with immunotherapies and other treatment strategies.

Reference

1. McArthur GA, Maio M, Arance A, et al. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol. 2016 Dec 19. doi: 10.1093/annonc/mdw641 [Epub ahead of print]