(ChemotherapyAdvisor) – The addition of sorafenib to first-line gemcitabine/cisplatin in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) did not meet the primary end point of improved overall survival (OS) when compared with gemcitabine/cisplatin alone, results of a phase 3 randomized, double-blind, placebo-controlled trial concluded in the Journal of Clinical Oncology online July 30, 2012.

A total of 904 patients with unresectable stage IIIB to IV NCSLC were randomly assigned to sorafenib 400mg twice daily or matching placebo plus gemcitabine (1,250mg/m2/day days 1 and 8 and cisplatin 75mg/m2 on day 1) for up to six, 21-day cycles between February 2007 and March 2009, Luis G. Paz-Ares, MD, PhD, Hospital Universitario Virgen del Rocío, Instituto de Investigaciones Biome´dicas de Sevilla, Seville, Spain, reported on behalf of the NSCLC Research Experience Utilizing Sorafenib (NExUS) Investigators Study Group.

In February 2008, patients with squamous cell histology were withdrawn from the study and excluded from analysis based on safety findings from the Evaluation of Sorafenib, Carboplatin and Paclitaxel Efficacy in NSCLC (ESCAPE) trial.

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Median OS was found to be similar in the sorafenib (n=385) and placebo (n=387) arms, 12.4 vs 12.5 months (HR 0.98; P=0.401). By investigator assessment, sorafenib improved median progression-free survival (PFS) and time-to-progression (TTP), both secondary end points; PFS was 6.0 vs 5.5 months (HR 0.83; P=0.008) and TTP (6.1 vs 5.5 months; HR 0.73; P<0.001).

Drug-related grade 3 or 4 adverse events that occurred more than twice as frequently in the sorafenib arm included hand-foot skin reaction (8.6% vs 0.3%), fatigue (7.3% vs 3.6%), rash (5.7% vs 0.5%), and hypertension (4.2% vs 1.8%).

“Although the addition of sorafenib to platinum-doublet chemotherapy agents has generally not resulted in patient benefits, sorafenib monotherapy has shown efficacy in phase II trials in patients with NSCLC, and phase III trials are underway,” the investigators concluded, adding that “the identification of biomarkers is crucial for the further development of sorafenib in patients with advanced NSCLC. In the absence of data delineating biomarkers that can predict the efficacy of sorafenib plus chemotherapy in subpopulations of these patients, further development of these combinations may not be warranted.”