MO29-1 The relationship between EGFR variant allele frequency and efficacy of osimertinib in EGFR mutation-positive NSCLC

The Oncomine Dx Target Test CDx system (oncomine) is used as an oncogene test for non-small cell carcinoma (NSCLC). Variant allele frequency (VAF) of oncogene is different in each epidermal growth factor receptor (EGFR) mutation-positive case. Association between VAF of EGFR and progression-free survival (PFS) of the first-generation EGFR-tyrosine kinase inhibitor (TKI) was reported previously. This retrospective study evaluated the relationship between VAF and the efficacy of Osimertinib as the first EGFR-TKI of each case. A total of 21 NSCLC patients who had been diagnosed as EGFR mutation-positive and been administrated Osimertinib as the first EGFR-TKI between September 2019 to June 2021 at Kanagawa Cancer Center were included on this retrospective study. Univariate analysis was performed using the Mann-Whitney U-test and the chi-square test. Comparison of the survival curves between the two groups was performed by the log-rank test. The median age was 63 years (range 40-84), 9 males, the histology of all cases were adenocarcinoma, 12 patients had EGFR exon 19 deletion (del19) and 9 patients had EGFR exon 21 L858R point mutations (L858R). The median PFS in the VAF 0.25 > group was 8.4 months [95% confidence interval (CI): 0.4 months - not reached], and the median PFS in the VAF 0.25 ≤ group was not reached [95% CI: 7.0 months - not reached], with significantly longer PFS in the VAF 0.25 ≤ group (p = 0.032, hazard ratio 4.9 [95% CI: 0.86-28.2]). The response rate in the VAF 0.25 > group was 36.8%, compared with 63.2% in the VAF 0.25 ≤ group (p = 0.31). The del19 group tended to have higher VAF than the L858R group, but there was no significant difference between the two groups (p = 0.48). In this study, low VAF was associated with poor PFS of Osimertinib. The results of EGFR mutation using oncomine may be useful to focus on VAF.