The Thai Cancer, 2021, 31.64.008
Abstract
Backgrond: The most common resistance mechanism to 1 st - or 2 nd -generation EGFR
tyrosine kinase inhibitor (TKI) in EGFR-mutant non-small cell lung cancer (NSCLC) patients is the
T790M mutation which confers a sensitivity to osimertinib. However, there are limited and
inconclusive data regarding predictive factors for the acquired T790M mutation.
Objective: The aim of this study was to identify clinical factors associated with secondary T790M
mutation in this population.
Method: We performed a retrospective study in sensitizing EGFR-mutation, exon 19 deletion or
exon 21 L858R point mutation, advanced NSCLC patients who had disease progression following
treatment with 1st - or 2nd -generation EGFR-TKI. The primary outcome was to identify clinical
parameters associated with the secondary T790M mutation.
Results: We recruited 207 EGFR-mutant lung cancer patients who were diagnosed and received
1st - or 2nd - generation EGFR-TKI between November 2011 and March 2020 and had disease
progression. We found the T790M mutation in 138 of 207 patients, 66.7%. With univariate analysis,
occurrence of T790M mutation was significantly associated with prior response to EGFR-TKI (OR
2.74, p = 0.006) and progression-free survival longer than 6 months (OR 3.71, p = 0.001).
However, only the prior response to EGFR-TKI remained the factor significantly associated with
T790M mutation under multivariate analysis (OR 2.61, p = 0.009). The median overall survival in
T790M positive patients was 41.9 months, which was longer than those of T790M negative
patients, 20.1 months (log rank p-value < 0.001).
Conclusion: Prior response to EGFR-TKI was the factor significantly associated with secondary
T790M mutation in patients with EGFR-mutant advanced NSCLC upon disease progression
following treatment with 1st - or 2nd - generation EGFR-TKI.