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N Engl J Med. 2015 Aug 20;373(8):726-36. doi: 10.1056/NEJMoa1502309.

Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations.

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From Memorial Sloan Kettering Cancer Center, New York (D.M.H., E.L.D., J.B.); Vanderbilt University Medical Center, Nashville (I.P., E.C.); University of Texas M.D. Anderson Cancer Center, Houston (V.S.); Massachusetts General Hospital, Boston (J.E.F., N.S.R.); Royal Marsden Hospital, Sutton, Surrey, United Kingdom (I.C.); Centre Léon Bérard, Lyon (J.-Y.B.), Institut Gustave Roussy, Villejuif (A.H.), Centre François Baclesse, Centre Hospitalier Universitaire Côte de Nacre, Caen (R.G.), and Institut Bergonié Cancer Center, Bordeaux (A.I.) - all in France; University Hospital of Cologne, Cologne (J.W.), Universitätsmedizin Mannheim, Mannheim (R.-D.H.), West German Cancer Center, University Hospital Essen, Essen (M.S.), and German Cancer Consortium, Heidelberg (M.S.) - all in Germany; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona (M.E.E.-F., J.T.), and Hospital Universitario Madrid Sanchinarro, Madrid (M.H.) - both in Spain; and F. Hoffmann-La Roche, Basel, Switzerland (S.F.L., M.M., F.S., M.L.V.).



BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers.


We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival.


In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma.


BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; number, NCT01524978.).

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