Efficacy and resistance of EGFR-TKIs for first-line treatment for compound EGFR mutations positive non-small cell lung cancer

Objective To observe the characteristics of mutation patterns in patients with compound EGFR mutations in the same exon and their resistance to EGFR TKIs, and to explore the clinical features and survival benefits among these non-small cell lung cancer (NSCLC) patients. Methods The survival benefits of 22 patients with compound EGFR mutations in the same exon were analyzed retrospectively Guangdong Lung Cancer Institute from January 2010 to April 2019, and the efficacy of targeted therapy was evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1. Next generation sequencing (NGS) technology was used to analyze the mutations of 8 patients at the baseline and 11 patients after the first-line EGFR TKIs. Results Among the enrolled 22 patients, there were 15 cases of compound mutation in exon 21, 6 cases in exon 18, and only 1 case in exon 19. The median progression free survival (mPFS) was 9.9 months for the whole group, 9.5 months for the patients with exon 21 compound mutation, and 5.4 months in those with exon 18. The Kaplan-Meier survival curve showed that there might be a trend of difference in PFS between the 2 groups, but there was no statistical significance (P=0.27). The mPFS of the first generation EGFR TKIs group and the second generation EGFR TKIs group were 13.8 and 9.7 months, respectively, with no significant difference (P=0.48). NGS results showed that 88% of compound EGFR mutations had TP53 concomitant mutations at baseline, and 25% had NQO1 and XRCC1 mutations. After first-line EGFR TKIs resistance, 50% of the patients had T790M mutation and 25% had MET amplification. The expression profile of drug resistance genes showed individual differences. In addition, the efficacy of osimertinib for acquired T790M mutation in patients with compound mutation of exon 19 was better than that of exon 21. Conclusion Among different exons, the efficacy of targeted therapy in patients with compound EGFR mutations may be different, but the efficacy of the first and second generation EGFR TKIs is similar, and the profiles of drug resistance genes are similar to those of classic EGFR sensitive monomutations.