Abstract
The most common event responsible for resistance to first- and second-generation (1st and 2nd) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is acquisition of T790M mutation. We examined whether T790M is related to clinicopathologic or prognostic factors in patients with relapse of EGFR mutant non-small cell lung cancer (NSCLC) after treatment with 1st or 2nd EGFR-TKIs. We retrospectively reviewed the T790M status and clinical characteristics of 73 patients with advanced or recurrent NSCLC who had been treated with EGFR-TKIs and undergone rebiopsy at Kurume University Hospital between March 2005 and December 2015. T790M mutation was more frequent in patients with EGFR exon 19 deletion mutation (63%, 26/41) than in those with L858R mutation (38%, 12/32) (p = 0.035). The median total duration of 1st or 2nd EGFR-TKI treatment was significantly longer in patients with T790M mutation than in those without (15.3 months vs 8.1 months, p < 0.001). Multivariate analysis revealed that the type of EGFR mutation and the total duration of EGFR-TKI treatment were significantly associated with T790M prevalence. Patients with EGFR exon 19 deletion mutation who receive long-term EGFR-TKI therapy show a high prevalence of T790M mutation. The present data are potentially important for clinical decision-making in NSCLC patients with EGFR mutation.
Highlights
Important predictive marker for 3rd epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI); determining the clinicopathologic characteristics of T790M-harboring non-small cell lung cancer (NSCLC) showing relapse after EGFR-TKI therapy is of high clinical relevance
It has become clear that T790M mutation-positive NSCLC shows a high rate of response to 3rd EGFR-TKIs11–13
It is important to determine the characteristics of NSCLCs harboring T790M mutation showing relapse after treatment with 1st or 2nd EGFR-TKIs, as these could have a great impact on treatment strategy
Summary
Important predictive marker for 3rd EGFR-TKIs; determining the clinicopathologic characteristics of T790M-harboring NSCLC showing relapse after EGFR-TKI therapy is of high clinical relevance. The median PFS after initial EGFR-TKI treatment was longer in the T790M mutation-positive group (13.6 months, 95% CI: 9.2–15.8) than in the negative group (7 months, 95% CI: 3.7–8.5) (p = 0.037).
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