Clinical Likelihood of Sporadic Primary EGFR T790M Mutation in EGFR-Mutant Lung Cancer

The clinical profile of EGFR-mutant lung cancer carrying sporadic primary EGFR T790M mutation was similar to that of classic EGFR-mutant lung cancer, except for an overrepresentation of never-smokers and brain metastasis. Additionally, any cytotoxic drugs showed no increased sensitivity for this mutant tumor. Thus, novel treatment strategies including T790M-targeting drugs are required to improve the efficacy of EGFR-TKIs in this population. Background: It has been reported that the presence of pretreatment EGFR T790M mutation may reduce the efficacy to EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancer. However, clinicopathologic features related to the likelihood of T790M mutation before treatment remains unknown. Patients and Methods: DNA from 124 pretreatment tissue samples from patients with advanced non-small-cell lung cancer carrying sensitive EGFR mutations was genotyped for EGFR T790M mutation with mass spectrometry. We compared the characteristics of 24 T790M patients and 100 patients with no or a low-level T790M mutation. Results: There were no differences in age, sex, histology, or initial stage between T790M and non/low T790M groups. However, there were significantly more never-smokers in the T790M group (P = .017). Brain metastasis was also more common in the T790M group (P = .036). The response rates to platinum, taxane, gemcitabine, and pemetrexed did not differ between the 2 groups. In the T790M group, the response rates were not significantly different among the 4 cytotoxic drugs (P = .809). The median time to progression during EGFR-TKI therapy was shorter in the T790M group than in the non/low T790M group (4.1 vs. 11.5 months, respectively; P < .001). The median overall survival from the start of first-line treatment of advanced disease was similar in both groups (31.5 vs. 36.0 months, respectively; P = .310). Conclusion: The clinical features of EGFR T790M-mutant lung cancer were similar to those of sensitive EGFR-mutant lung cancer, except for the overrepresentation of never-smokers and brain metastasis. (C) 2015 Elsevier Inc. All rights reserved.