Phase III Study of Carboplatin and Paclitaxel Alone or With Sorafenib in Advanced Non Small-Cell Lung Cancer
Phase III Study of Carboplatin and Paclitaxel Alone or With Sorafenib in Advanced Non Small-Cell Lung Cancer
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DOI：
10.1200/jco.2009.26.1321
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发表时间：
2010-04-10
影响因子：
45.3
通讯作者：
Hanna, Nasser
中科院分区：
文献类型：
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作者：
Scagliotti, Giorgio;Novello, Silvia;Hanna, Nasser
目的：本项多中心、随机、安慰剂对照的I/F期临床试验评估了口服多激酶抑制剂索拉非尼的疗效和安全性，联合卡铂和紫杉醇治疗未经化疗的IIIB或IV期非小细胞肺癌（NSCLC）患者。6名患者被随机分配接受最多6个21天周期的卡铂曲线下面积6和紫杉醇200 mg/m2（CP）（第1天），随后在第2 - 19天给予索拉非尼B 400 mg每日两次（n = 464，A组）或安慰剂（n = 462，B组）。CP后的维持期包括索拉非尼400 mg或安慰剂，每日两次。主要终点是总生存期（OS）;次要终点包括无进展生存期和肿瘤responsibility.Results的总体人口统计学之间的武器平衡; 223例（24%）鳞状细胞组织学。根据计划的中期分析，A组的中位OS为10.7个月，B组为10.6个月（风险比[HA] = 1.15; 95% CI，0.94 - 1.41; P = 0.915）。在中期分析得出结论认为该研究极不可能达到其主要终点后，终止了该研究。预先设定的探索性分析显示，A组鳞状细胞组织学患者的死亡率高于B组（HR = 1.85; 95% CI，1.22 - 2.81）。索拉非尼3 ~ 4级毒性反应主要为皮疹（8.4%）、手足皮肤反应（7.8%）和腹泻（3.5%）。
Purpose This phase If, multicenter, randomized, placebo controlled trial assessed the efficacy and safety of sorafenib, an oral multikinase inhibitor, in combination with carboplatin and paclitaxel in chemotherapy naive patients with unresectable stage IIIB or IV non small-cell lung cancer (NSCLC).Patients and Methods Nine hundred twenty-six patients were randomly assigned to receive up to six 21 day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2) (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day. The primary end point was overall survival (OS); secondary end points included progression free survival and tumor response.Results Overall demographics were balanced between arms; 223 patients (24%) had squamous cell histology. On the basis of a planned interim analysis, median OS was 10.7 months in arm A and 10.6 months in arm B (hazard ratio [HA] = 1.15; 95% Cl, 0.94 to 1.41; P = .915). The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point. A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B (HR = 1.85; 95% Cl, 1.22 to 2.81). Main grade 3 or 4 sorafenib-related toxcities included rash (8.4%), hand-foot skin reaction (7.8%), and diarrhea (3.5%).Conclusion No clinical benefit was observed from adding sorafenib to CA chemotherapy as first-line treatment for NSCLC.