Vemurafenib showed promising activity against several nonmelanoma cancers carrying BRAF V600 mutations in a preliminary phase II study reported online Aug. 20 in the New England Journal of Medicine.

Vemurafenib, a selective oral inhibitor of the BRAF V600 kinase, has produced a 50% response rate and improved survival in patients with metastatic melanoma expressing BRAF V600 mutations. Researchers subsequently identified the same mutations in numerous other tumor types, many of which are aggressive and some of which have no effective treatment. But the drug’s efficacy against these malignancies has not been examined systematically until now, because of “the large number of tumor types involved, the low frequency of BRAF V600 mutations, and the rarity of some of the cancers,” said Dr. David M. Hyman of Memorial Sloan Kettering Cancer Center, New York, and his associates.

To perform such an exploratory investigation, Dr. Hyman and his colleagues used a “basket” study design allowing enrollment of 122 patients from 23 medical centers worldwide who had advanced BRAF-V600–positive non–small cell lung cancer, ovarian cancer, colorectal cancer, cholangiocarcinoma, breast cancer, multiple myeloma, Erdheim-Chester disease, Langerhans-cell histiocytosis, anaplastic thyroid cancer, or “other” malignancies. A total of 95 of these participants received vemurafenib monotherapy, and 27 who had colorectal cancer received vemurafenib plus cetuximab combination therapy.

After 8 weeks of treatment, many patients showed partial or complete responses. Continued treatment often yielded tumor regression and prolonged stabilization of disease. The agent was particularly effective against non–small cell lung cancer, with an objective response rate of 42% among 19 evaluable patients, and against Erdheim-Chester disease and Langerhans-cell histiocytosis, with an objective response rate of 43% among 14 evaluable patients. The latter two malignancies are closely related orphan diseases with no approved therapies; none of these patients showed disease progression while taking vemurafenib, Dr. Hyman and his associates said (New Engl. J. Med. 2015 Aug 20 [doi:10.1056/NEJMoa1502309]).

Vemurafenib also showed modest but promising activity against anaplastic thyroid cancer, cholangiocarcinoma, anaplastic pleomorphic xanthoastrocytoma, salivary-duct cancer, clear-cell sarcoma, low-grade serous ovarian cancer, high-grade glioblastoma, anaplastic ependymoma, pancreatic cancer, and carcinoma of unknown primary type. Most of these cancers have limited therapeutic options. However, these results must be interpreted with caution because the largest of these subgroups of patients only comprised 8 patients.