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.

Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J, Zhang L, Liao M, Sun Y, Gans S, Syrigos K, Le Marie E, Gottfried M, Vansteenkiste J,Alberola V, Strauss UP, Montegriffo E, Ong TJ, Santoro A.

Source

Luis G. Paz-Ares, Hospital Universitario Virgen del Rocío/Universidad de Sevilla/ Consejo Superior de Investigaciones Cientificas, Seville; Vincente Alberola, Hospital Arnau de Vilanova, Valencia, Spain; Bonne Biesma, Jeroen Bosch Hospital, 's-Hertogenbosch; Steven Gans, St. Jansdal, Harderwijk, the Netherlands; David Heigener, Krankenhaus Grosshansdorf, Grosshansdorf; Joachim von Pawel, Asklepios Fachkliniken, Gauting; Uwe Phillip Strauss, Bayer Schering Pharma, Leverkusen, Germany; Timothy Eisen, Cambridge Biomedical Research Centre, Cambridge; Elaine Montegriffo, Bayer HealthCare, Newbury, United Kingdom; Jaafar Bennouna, Centre Rene Gauducheau, Saint Herblain; Etienne Le Marie, Bretonneau-Tours, Tours, France; Li Zhang, Sun Yat-sen University Cancer Hospital, Guangzhou, Guangdong; Meilin Liao, Shanghai Chest Hospital, Shanghai; Yan Sun, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China; Kostas Syrigos, Athens School of Medicine, Athens, Greece; Maya Gottfried, Meir Medical Center, Kfar Saba, Israel; Johan Vansteenkiste, University Hospital Gasthuisberg, Leuven, Belgium; Teng Jin Ong, Bayer HealthCare Pharmaceuticals, Montville, NJ; and Armando Santoro, Humanitas Cancer Center, Rozzano, Milan, Italy.

Abstract

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of Sorafenib, Carboplatin and Paclitaxel Efficacy in NSCLC (ESCAPE) trial, patients with squamous cell histology were withdrawn from the trial in February 2008 and excluded from analysis.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.

TimAllenMDJD

Thursday, August 2, 2012