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Vemurafenib produces response in brain metastatic melanoma
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Vemurafenib showed a clinically meaningful response rate among patients with BRAFV600-mutated melanoma with brain metastases, according to findings published in Annals of Oncology.
Further, the drug was well-tolerated and did not show significant central nervous system toxicity.
“Both targeted therapies and immune checkpoint inhibitors improve OS in patients with advanced melanoma and for targeted therapies even longer survival is obtained with combinations of BRAF and MEK inhibitors in patients with BRAFV600 mutations,” Grant A. McArthur, PhD, FRACP, of the Peter MacCallum Canter Centre, East Melbourne, Australia, and colleagues wrote. “The BRAF inhibitor vemurafenib is less well studied in patients with brain metastases.”
McArthur and colleagues enrolled 146 patients (62% male) — from Australia, Canada, France, Germany, Israel, Italy, Netherlands, Spain, the United Kingdom and the United States — with BRAFV600-mutated melanoma with brain metastases.
Patients were assigned to two cohorts based on whether their brain metastases were previously untreated (n = 90) or treated (n = 56). Patients received treatment with 960 mg of vemurafenib twice per day until disease progression or intolerance.
ORR in the brain among patients in the untreated cohort served as the primary outcome.
Median time since diagnosis was 1 month in the untreated cohort, and 4.2 months in the previously treated cohort. Median duration of treatment for both groups was 4.1 months, and 84% of patients died during the study.
Extracranial response rate was 33% among previously untreated patients and 23% in the previously treated group. The previously untreated group had a median PFS of 3.7 months and a median OS of 8.9 months, and patients with previous treatment had a median PFS of 4 months and a median OS of 9.6 months. Fifty-nine patients (66%) in the previously untreated cohort experienced grade 3 or 4 adverse events, compared with 36 (64%) of the previously treated cohort.
“The study demonstrates clinically meaningful response rates of melanoma brain metastases to vemurafenib, which was well tolerated without significant intracranial toxicity,” the researchers wrote.
McArthur and colleagues advised caution in interpreting the findings, however, because of the small cohort.
“The development of combined BRAF and MEK inhibition as a new standard of care for patients with BRAF-mutated melanoma offers further options for patients with brain metastases, and clinical data on these combination therapies are awaited,” they wrote. “Further innovation is still needed for patients with brain metastases, including evaluation of immunotherapies and other approaches in combination with BRAF-pathway inhibition.” – by Andy Polhamus
Disclosure: McArthur reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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