Lay Summary:Nexavar has not been proven to be effecive for melanoma.
Nexavar has not been proven to be effective for melanoma. A Phase III trial administering Nexavar® (sorafenib) or placebo tablets in combination with the chemotherapeutic agents carboplatin and paclitaxel in patients with advanced melanoma did not meet its primary endpoint of improving progression-free survival (PFS). The treatment effect was comparable in each arm. The international Phase III, double-blind, randomized, placebo-controlled trial evaluated Nexavar when administered in combination with a standard dosing schedule (21-day cycles) of carboplatin and paclitaxel. Two hundred seventy patients progressing after one previous systemic chemotherapeutic treatment (with either dacarbazine (DTIC) or temozolomide) were enrolled into the study. The study was designed to measure the safety and efficacy of Nexavar when co-administered with chemotherapy, and had PFS as its primary endpoint. PFS is defined as the time that a patient lives without meaningful tumor growth. The safety profile of these agents in combination (Nexavar with carboplatin/paclitaxel) was comparable to those previously reported for these agents in combination. Preliminary results from a randomized Phase II study of a Temodar and Nexavar combination shows promise. An abstract showing effectiveness of Nexavar and dacarbaxine was presented in the 2007 ASCO meeting. randomized, 17-center, phase II study of 101 chemotherapy-naive patients showed a 50% improvement in progression-free survival and a 62% improvement in time to progression when sorafenib (Nexavar) was added to dacarbazine (DTIC-Dome) compared with dacarbazine plus placebo. Improved progression-free survival did not translate into a survival benefit, however. Thus, for now, Nexavar with Temodar or IV dacarbazine there are two phase 2 studies that show effectveness for melanoma. A recent review said this: “However, as a single-agent therapy, sorafenib seems to be of limited use. Also, the combination of sorafenib with the chemotherapeutic agents carboplatin and paclitaxel has failed to show superiority in progression-free and overall survival compared to the same chemoregimen plus an oral placebo in a phase III trial (PRISM study). More promising data were observed in large-sized phase II studies on dacarbazine (DTIC) plus sorafenib and temozolomide plus sorafenib. Recently reported was a study in which, 101 patients with advanced stages of melanoma were randomly assigned to receive either chemotherapy alone with the drug dacarbazine or dacarbazine plus Nexavar. Patients who received both dacarbazine and Nexavar experienced an average time until disease progression that was nearly double the time experienced by those treated with dacarbazine alone (12 weeks versus 21 weeks). Overall survival among patients who received both dacarbazine and Nexavar was also improved compared with those treated with dacarbazine only (51 weeks versus 46 weeks). The place of nexavar is not yet estabished in the treatment of melanoma and it is still investigational.
McDermott, DF., Sosman, JA., Gonzalez, R, et al. Double blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: A report from the 11715 Study group. Journal of Clinical Oncology. 2008;26:2178-2185.
Egberts F, Kahler KC, Livingstone E, Hauschild A..Metastatic melanoma: scientific rationale for sorafenib treatment and clinical results.Onkologie. 2008 Jul;31(7):398-403 http://www.oncologyreport.com/melanoma/70994b.html