Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Gemcitabine/Cisplatin Alone or With Sorafenib for the First-Line Treatment of Advanced, Nonsquamous Non-Small-Cell Lung Cancer

被引：208

作者：

Paz-Ares, Luis G. ^{[1
]}

Biesma, Bonne ^{[3
]}

Heigener, David ^{[5
]}

von Pawel, Joachim ^{[6
]}

Eisen, Timothy ^{[8
]}

Bennouna, Jaafar ^{[10
]}

Zhang, Li ^{[12
]}

Liao, Meilin ^{[13
]}

Sun, Yan ^{[14
]}

Gans, Steven ^{[4
]}

Syrigos, Kostas ^{[15
]}

Le Marie, Etienne ^{[11
]}

Gottfried, Maya ^{[16
]}

Vansteenkiste, Johan ^{[17
]}

Alberola, Vincente ^{[2
]}

Strauss, Uwe Phillip ^{[7
]}

Montegriffo, Elaine ^{[9
]}

Ong, Teng Jin ^{[18
]}

Santoro, Armando ^{[19
]}

机构：

[1] Univ Seville, Hosp Univ Virgen del Rocio, Dept Med Oncol, Inst Invest Biomed Sevilla,CSIC, Seville 41013, Spain

[2] Hosp Arnau Vilanova, Valencia, Spain

[3] Jeroen Bosch Hosp, sHertogenbosch, Netherlands

[4] St Jansdal, Harderwijk, Netherlands

[5] Krankenhaus Grosshansdorf, Grosshansdorf, Germany

[6] Asklepios Fachkliniken, Gauting, Germany

[7] Bayer Schering Pharma, Leverkusen, Germany

[8] Cambridge Biomed Res Ctr, Cambridge, England

[9] Bayer HealthCare, Newbury, Berks, England

[10] Ctr Rene Gauducheau, St Herblain, France

[11] Bretonneau Tours, Tours, France

[12] Sun Yat Sen Univ, Canc Hosp, Guangzhou 510275, Guangdong, Peoples R China

[13] Shanghai Chest Hosp, Shanghai, Peoples R China

[14] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China

[15] Athens Sch Med, Athens, Greece

[16] Med Ctr, Kefar Sava, Israel

[17] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium

[18] Bayer HealthCare Pharmaceut, Montville, NJ USA

[19] Humanitas Canc Ctr, Milan, Italy

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2012年 / 30卷 / 25期

关键词：

RAF/MEK/ERK PATHWAY; PLUS GEMCITABINE; I TRIAL; ERLOTINIB; CARBOPLATIN; CHEMOTHERAPY; BEVACIZUMAB; COMBINATION; PACLITAXEL; CISPLATIN;

D O I：

10.1200/JCO.2011.39.7646

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose This trial evaluated the efficacy and safety of sorafenib plus gemcitabine/cisplatin in chemotherapy-naive patients with unresectable stage IIIB to IV nonsquamous non-small-cell lung cancer (NSCLC). Patients and Methods Between February 2007 and March 2009, 904 patients were randomly assigned to daily sorafenib (400 mg twice a day) or matching placebo plus gemcitabine (1,250 mg/m(2) per day on days 1 and 8) and cisplatin (75 mg/m(2) on day 1) for up to six 21-day cycles. Because of safety findings from the Evaluation of Sorafenib, Carboplatin and Paclitaxel Efficacy in NSCLC (ESCAPE) trial, patients with squamous cell histology were withdrawn from the trial in February 2008 and excluded from analysis. The primary end point was overall survival (OS), and secondary end points included progression-free survival (PFS) and time-to-progression (TTP). Results The primary analysis population consisted of 772 patients (sorafenib, 385; placebo, 387); the two groups had similar demographic and baseline characteristics. Median OS was similar in the sorafenib and placebo groups (12.4 v 12.5 months; hazard ratio [HR], 0.98; P = .401). By investigator assessment, sorafenib improved median PFS (6.0 v 5.5 months; HR, 0.83; P = .008) and TTP (6.1 v 5.5 months; HR, 0.73; P < .001). Grade 3 to 4 drug-related adverse events more than two-fold higher in the sorafenib group included hand-foot skin reaction (8.6% v 0.3%), fatigue (7.3% v 3.6%), rash (5.7% v 0.5%), and hypertension (4.2% v 1.8%). No unexpected toxicities were observed. Conclusion This study did not meet its primary end point of improved OS when sorafenib was added to first-line gemcitabine/cisplatin in patients with advanced nonsquamous NSCLC. Identification of predictive biomarkers is warranted in future trials of sorafenib. J Clin Oncol 30: 3084-3092. (C) 2012 by American Society of Clinical Oncology

引用

页码：3084 / 3092

页数：9

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