Association Between EGFR T790M Status and Progression Patterns During Initial EGFR-TKI Treatment in Patients Harboring EGFR Mutation

Progression patterns at the time of resistance to the initial epidermal growth factor receptor (EFGR)-tyrosine kinase inhibitors are clinically heterogeneous. The associations between progression patterns and the EGFR T790M mutation have not been elucidated. In this study, we found that solitary lesion progression at the time of failure of the initial treatment with EGFR-tyrosine kinase inhibitors is significantly associated with a T790M mutation status by multivariate analysis. Background Emergence of the T790M point mutation in exon 20 of the epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study was to investigate the association between T790M mutation status and the progression patterns during EGFR-TKI treatment. Methods We reviewed 181 patients with advanced non–small-cell lung cancer harboring EGFR mutation, who were evaluated for T790M mutation status after initial EGFR-TKI failure (gefitinib, erlotinib, or afatinib). We retrospectively investigated the patient characteristics, initial EGFR-TKI response, T790M mutation status, subsequent treatment after initial EGFR-TKIs, timing of re-biopsy, and progression patterns during the EGFR-TKI treatment. Results After the resistance to the EGFR-TKIs, the T790M mutation was identified in 87 (48%) of 181 patients. Seventy-three (40%) patients had solitary lesion progression, and 108 (60%) had multiple lesion progression during the initial EGFR-TKI treatment. The prevalence of the T790M mutation was significantly greater in patients with solitary lesion progression than those with multiple lesion progression (58% vs. 24%; P <.0001). The overall response rate and progression-free survival on initial EGFR-TKIs were significantly better in patients who acquired T790M after failure of EGFR-TKIs than those without T790M (overall response rate, 80% vs. 60%; P =.0033 and progression-free survival, 11.4 vs. 9.3 months; P =.0050). The multivariate analysis showed that gender, initial EGFR-TKI response, and progression patterns were significantly associated with T790M mutation status. Discussion The progression patterns during initial EGFR-TKIs and initial EGFR-TKI response are associated with the T790M mutation.