Originally published as JCO Early Release 10.1200/JCO.2007.15.7636 on April 6 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Hauschild, A. Articles by Keilholz, U. PubMed PubMed Citation Articles by Hauschild, A. Articles by Keilholz, U. Social Bookmarking                            What's this?

Results of a Phase III, Randomized, Placebo-Controlled Study of Sorafenib in Combination With Carboplatin and Paclitaxel As Second-Line Treatment in Patients With Unresectable Stage III or Stage IV Melanoma

Axel Hauschild, Sanjiv S. Agarwala, Uwe Trefzer, David Hogg, Caroline Robert, Peter Hersey, Alexander Eggermont, Stephan Grabbe, Rene Gonzalez, Jens Gille, Christian Peschel, Dirk Schadendorf, Claus Garbe, Steven O'Day, Adil Daud, J. Michael White, Chenghua Xia, Kiran Patel, John M. Kirkwood, Ulrich Keilholz

From the University of Kiel, Kiel; Charité Berlin; University Hospital Benjamin Franklin, Berlin; Johannes Gutenberg Clinic-Mainz University, Mainz, Germany; Johann Wolfgang Goethe University, Frankfurt am Main; Klinikum rechts der Isar, Munich; University Hospital of Mannheim, Mannheim, Germany; University Hospital of Tuebingen, Tuebingen, Germany; St Luke's Hospital and Health Network, Bethlehem; University of Pittsburgh Cancer Institute, Pittsburgh, PA; University of Colorado Cancer Center, Aurora, CO; The Angeles Clinic and Research Institute, Santa Monica; Onyx Pharmaceuticals, Emeryville, CA; H. Lee Moffitt Cancer Center, Tampa, FL; Bayer AG, West Haven, CT; University of Toronto and Princess Margaret Hospital, Toronto, Ontario, Canada; Institut Gustave-Roussy, Villejuif Cedex, France; Newcastle Mater Misericordiae Hospital, Newcastle, New South Wales, Australia; and the Erasmus University Medical Center-Daniel den Hoed Cancer Centre, Rotterdam, Netherlands.

Corresponding author: Sanjiv S. Agarwala, MD, St Luke's Cancer Center, 801 Ostrum St, Bethlehem, PA 18015; e-mail: agarwas{at}slhn.org.

Purpose This phase III, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of sorafenib with carboplatin and paclitaxel (CP) in patients with advanced melanoma who had progressed on a dacarbazine- or temozolomide-containing regimen.

Patients and Methods A total of 270 patients were randomly assigned to receive intravenous paclitaxel 225 mg/m² plus intravenous carboplatin at area under curve 6 (AUC 6) on day 1 of a 21-day cycle followed by either placebo (n = 135) or oral sorafenib 400 mg (n = 135) twice daily on days 2 to 19. The primary efficacy end point was progression-free survival (PFS); secondary and tertiary end points included overall survival and incidence of best response, respectively.

Results The median PFS was 17.9 weeks for the placebo plus CP arm and 17.4 weeks for the sorafenib plus CP arm (hazard ratio, 0.91; 99% CI, 0.63 to 1.31; two-sided log-rank test P = .49). Response rate was 11% with placebo versus 12% with sorafenib. Dermatologic events, grade 3 thrombocytopenia, diarrhea, and fatigue were more common in patients treated with sorafenib plus CP versus placebo plus CP.

Conclusion In this study, the addition of sorafenib to CP did not improve any of the end points over placebo plus CP and cannot be recommended in the second-line setting for patients with advanced melanoma. Both regimens had clinically acceptable toxicity profiles with no unexpected adverse events. A trial of similar design for the first-line treatment of patients with advanced melanoma (intergroup trial E2603) is currently ongoing.

A.H. and S.S.A. contributed equally to this article.

Supported by Bayer AG and Onyx Pharmaceuticals, Inc.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Written on behalf of the 11718 study investigators.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org

Clinical trial information can be found for the following: NCT00111007 [ClinicalTrials.gov] .

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?