Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/916305

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Title
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
Author/Creator
Hauschild, Axel;  Agarwala, Sanjiv S;  Peschel, Christian;  Schadendorf, Dirk;  Garbe, Claus;  O'Day, Steven;  Daud, Adil;  White, J. Michael;  Xia, Chenghua;  Patel, Kiran;  Kirkwood, John M.;  Keilholz, Ulrich;  Trefzer, Uwe;  Hogg, David;  Robert, Caroline;  Hersey, Peter;  Eggermont, Alexander;  Grabbe, Stephan;  Gonzalez, Rene;  Gille, Jens
Institution
The University of Newcastle. Faculty of Health, School of Medicine and Public Health
Description
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.
Relation
Journal of Clinical Oncology Vol. 27, Issue 17, p. 2823-2830
Publisher Link
http://dx.doi.org/10.1200/jco.2007.15.7636
Date
2009
Publisher
American Society of Clinical Oncology
Keyword(s)
sorafenib;  carboplatin and paclitaxel;  melanoma;  placebo-controlled studies;  dacarbazine;  temozolomide
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/916305
Identifier
ISSN:0732-183X
Reviewed
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Subject
"Journal of Clinical Oncology"
 
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