• Josep Tabernero, Rocio Garcia-Carbonero, James Cassidy, Alberto Sobrero, Eric Van Cutsem, Claus-Henning Köhne, Sabine Tejpar, Oleg Gladkov, Irina Davidenko, Ramon Salazar, Liubov Vladimirova, Sergey Cheporov, Olga Burdaeva, Fernando Rivera, Leslie Samuel, Irina Bulavina, Vanessa Potter, Yu-Lin Chang, Nathalie A Lokker, and Peter J O'Dwyer.
• Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain. jtabernero@vhio.net
• Clin Cancer Res. 2013 May 1; 19 (9): 2541-50.

PurposeThis randomized, double-blind, placebo-controlled, phase IIb study evaluated adding sorafenib to first-line modified FOLFOX6 (mFOLFOX6) for metastatic colorectal cancer (mCRC).Experimental DesignPatients were randomized to sorafenib (400 mg b.i.d.) or placebo, combined with mFOLFOX6 (oxaliplatin 85 mg/m(2); levo-leucovorin 200 mg/m(2); fluorouracil 400 mg/m(2) bolus and 2400 mg/m(2) continuous infusion) every 14 days. Primary endpoint was progression-free survival (PFS). Target sample was 120 events in 180 patients for >85% power (two-sided α = 0.20) to detect an HR = 0.65.ResultsOf 198 patients randomized, median PFS for sorafenib plus mFOLFOX6 was 9.1 months versus 8.7 months for placebo plus mFOLFOX6 (HR = 0.88; 95% CI, 0.64-1.23; P = 0.46). There was no difference between treatment arms for overall survival. Subgroup analyses of PFS and overall survival showed no difference between treatment arms by KRAS or BRAF status (mutant and wild type). The most common grade 3/4 adverse events in the sorafenib and placebo arms were neutropenia (48% vs. 22%), peripheral neuropathy (16% vs. 21%), and grade 3 hand-foot skin reaction (20% vs. 0%). Treatment discontinuation because of adverse events was 9% and 6%, respectively. Generally, dose intensity (duration and cumulative doses) was lower in the sorafenib arm than in the placebo arm.ConclusionThis study did not detect a PFS benefit with the addition of sorafenib to first-line mFOLFOX6 for mCRC. KRAS and BRAF status did not seem to impact treatment outcomes but the subgroups were small. These results do not support further development of sorafenib in combination with mFOLFOX6 in molecularly unselected patients with mCRC.©2013 AACR.

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