EGFR Mutation Status Might Predict Sorafenib Benefit in NSCLC

Bonnie Gillis
Published: Friday, Nov 30, 2012
Dr. Tony S. Mok

Tony S. Mok, MD

Results of the phase III MISSION trial presented at the 2012 ESMO Congress showed that third- or fourth-line treatment with sorafenib did not improve overall survival (OS) in patients with advanced non–small cell lung cancer (NSCLC). A post-hoc biomarker analysis of MISSION suggested that patients with EGFR-mutant tumors may benefit from treatment with sorafenib, but KRAS mutation status was not predictive of response.

“Mutated EGFR is a potent predictor for gefitinib. There was a hint in the biomarker analysis that it may be predictive for sorafenib, but interpret these data with caution,” said lead author Tony S. Mok, MD, Chinese University of Hong Kong. “The sample size is small, it was a subgroup analysis, and an exploratory analysis only.”

MISSION was a multinational, doubleblind, placebo-controlled, randomized phase III trial comparing sorafenib plus best supportive care versus best supportive care alone as third- or fourth-line therapy in an unselected population with NSCLC. The study enrolled 703 patients who were randomized 1:1 to either 400 mg of oral sorafenib twice daily or placebo.

Median overall survival was comparable between the sorafenib and placebo arms (248 vs 253 days; P = .4687), and thus the trial failed to reach its primary endpoint. Statistically significant improvements with sorafenib were demonstrated with several secondary endpoints, including median progression-free survival (PFS; P <.0001), time to disease progression (P <.0001), overall response rate (P <.001), and disease control rate (P <.0001).

Although the primary results were negative, the researchers conducted a mutational analysis involving 347 patients to determine if some patients might benefit from sorafenib. In the analysis subgroup, EGFR mutations were detected in 26% and KRAS mutations in 20%, and were well balanced between the two study arms.

The EGFR mutation analysis included 44 patients from the sorafenib group and 45 from the placebo group who had mutated EGFR in tumor or plasma, and 122 in the sorafenib group and 136 in the placebo group with wild-type EGFR.

EGFR Mutational Subanalysis
of Phase III Mission Trial

Treatment Median
PFS (mo)
OS (mo)
EGFR-mutant tumors
Sorafenib (n = 44) 2.7 13.9
Placebo (n = 45) 1.4 6.5
P value <.001 <.002
EGFR wild-type tumors
Sorafenib (n = 122) 2.7 8.3
Placebo (n = 136) 1.5 8.4
P value <.001 <.559

Mo indicates months; OS, overall survival; PFS, progression-free survival.

A significant PFS benefit was observed for sorafenib in patients with mutated EGFR: median PFS was 2.7 months with sorafenib versus 1.4 months with placebo (hazard ratio [HR] = .27; 95% CI, .16-.46; P <.001). PFS was also significantly better with sorafenib in wild-type EGFR patients versus the placebo group: median PFS of 2.7 months versus 1.5 months, respectively (HR = .62; 95% CI, .48-.82; P <.001).

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Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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