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
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
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DOI：
10.1200/jco.2007.15.7636
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发表时间：
2009-06-10
影响因子：
45.3
通讯作者：
Keilholz, Ulrich
中科院分区：
文献类型：
--
作者：
Hauschild, Axel;Agarwala, Sanjiv S.;Keilholz, Ulrich
目的本研究为III期、随机、双盲、安慰剂对照研究是为了评估索拉非尼与卡铂和紫杉醇（CP）在达卡巴嗪或替莫唑胺治疗方案进展的晚期黑色素瘤患者中的疗效和安全性。在21天周期的第1天静脉注射卡铂（AUC 6），然后在第2天至第19天每天两次口服安慰剂（n = 135）或索拉非尼400 mg（n = 135）。主要疗效终点为无进展生存期（PFS）;次要和第三终点包括总生存期和最佳反应的发生率，分别为ResultsThe中位PFS为17.9周安慰剂加CP组和17.4周索拉非尼加CP组（风险比，0.91; 99%CI，0.63至1.31;双侧对数秩检验P = 0.49）。安慰剂组的缓解率为11%，索拉非尼组为12%。皮肤病事件，3级血小板减少症，腹泻和疲劳更常见于索拉非尼加CP与安慰剂加CP治疗的患者。ConclusionIn这项研究中，索拉非尼加CP没有改善任何安慰剂加CP的终点，不能建议在二线设置为晚期黑色素瘤患者。两种方案均具有临床可接受的毒性特征，没有意外的不良事件。目前正在进行一项设计相似的晚期黑色素瘤患者一线治疗试验（组间试验E2603）。
PurposeThis 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 MethodsA total of 270 patients were randomly assigned to receive intravenous paclitaxel 225 mg/m(2) 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.ResultsThe 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.ConclusionIn 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.