Blank, C.U. (Christian U.)

Filtering

20121

Settings

Author search.filters.isAuthorOfPublication.2e0ea2db-925b-453d-8dc9-a21842bc0038

Search Results

Now showing 1 - 1 of 1
  • Thumbnail Image
    Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
    (Elsevier, 2012) Rutkowski, P. (Piotr); Martin-Algarra, S. (Salvador); Haney, P. (Patricia); Millward, M. (Michael); Goodman, V. (Vicki); Karaszewska, B. (Boguslawa); Swann, S. (Suzanne); Demidov, L.V. (Lev V.); Mauch, C. (Cornelia); Mirakhur, B. (Beloo); Chiarion-Sileni, V. (Vanna); Jouary, T. (Thomas); Chapman, P.B. (Paul B.); Grob, J.J. (Jean-Jacques); Miller, W.H. (Wilson H.); Blank, C.U. (Christian U.); Kaempgen, E. (Eckhart); Hauschild, A. (A.); Guckert, M.E. (Mary E.); Gutzmer, R. (Ralf); Martin, A.M. (Anne-Marie)
    Background: Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in studies of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma. We studied the efficacy of dabrafenib in patients with BRAF(V600E)-mutated metastatic melanoma. Methods: We enrolled patients in this open-label phase 3 trial between Dec 23, 2010, and Sept 1, 2011. This report is based on a data cutoff date of Dec 19, 2011. Patients aged 18 years or older with previously untreated, stage IV or unresectable stage III BRAF(V600E) mutation-positive melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m(2) intravenously every 3 weeks). Patients were stratified according to American Joint Committee on Cancer stage (unresectable III+IVM1a+IVM1b vs IVM1c). The primary endpoint was investigator-assessed progression-free survival and was analysed by intention to treat; safety was assessed per protocol. This study is registered with ClinicalTrials.gov, number NCT01227889. Findings: Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients). Median progression-free survival was 5·1 months for dabrafenib and 2·7 months for dacarbazine, with a hazard ratio (HR) of 0·30 (95% CI 0·18-0·51; p<0·0001). At data cutoff, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomised treatment. Treatment-related adverse events (grade 2 or higher) occurred in 100 (53%) of the 187 patients who received dabrafenib and in 26 (44%) of the 59 patients who received dacarbazine. The most common adverse events with dabrafenib were skin-related toxic effects, fever, fatigue, arthralgia, and headache. The most common adverse events with dacarbazine were nausea, vomiting, neutropenia, fatigue, and asthenia. Grade 3-4 adverse events were uncommon in both groups. Interpretation: Dabrafenib significantly improved progression-free survival compared with dacarbazine.