Relationship Between T790M Allele Frequency and Therapeutic Effects Before and After EGFR-TKI Administration Using...

This study aimed to investigate the effectiveness of sequential treatment with afatinib and osimertinib by clarifying the correlation between therapeutic effects and EGFR T790M mutant allele frequency.

From August 2013 to July 2019, tumor samples from before and after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) administration were collected from patients from eight institutions. We measured T790M mutant allele frequency using droplet digital polymerase chain reaction using biopsy specimens from patients mainly treated with afatinib and analyzed the T790M to EGFR-activating mutation ratio (T/A ratio) in pre- and post-biopsy tissue.

Among 36 patients (afatinib group: n=24, first-generation EGFR-TKI group: n=12) with preserved pre- and post-biopsy tissue, the median T/A ratios before (pre-T/A ratio) and after EGFR-TKI administration (post-T/A ratio) in the afatinib group were 0.005 and 0.014, and those in the first-generation EGFR-TKI group were 0.026 and 0.352, respectively. The results of a Mann-Whitney U-test revealed that the difference between the pre-T/A and post-T/A ratios was not higher in the afatinib group than in the first-generation EGFR-TKI (p=0.0372). No significant difference in progression-free or overall survival was found between the two groups.

Compared with first-generation EGFR-TKI treatment, treatment with afatinib did not affect changes in the T/A ratio.