TKIs less effective in lung cancer patients with complex EGFR mutations and primary drug-resistance patterns
First-generation EGFR tyrosine kinase inhibitor (TKI) therapy is less effective in patients with advanced lung adenocarcinoma who have complex EGFR mutations and primary drug-resistance patterns, according to results of a Chinese study reported at ELCC 2018.
The retrospective study included 5,898 patients diagnosed with EGFR mutation–positive lung adenocarcinoma between January 2011 and January 2017. Complex EGFR mutations (eg, two or more different EGFR mutations within a tumour sample) were identified in 187 patients (3.2 percent), 95 of whom had advanced lung adenocarcinoma and were treated with EGFR TKIs. [Zhang B, et al, ELCC 2018, abstract 140PD]
“Among 27 patients with Del-19+21L858R mutations, the objective response rate [ORR] with standard first-generation EGFR TKI therapy was 72.7 percent. The ORR in patients with Del-19/21L858R+ atypical mutation [n=28] and those with double atypical mutations [n=20] was 54.2 percent and 66.7 percent, respectively,” reported investigator Dr Bo Zhang of the Shanghai Chest Hospital in Shanghai, China.
Median progression-free survival (PFS) was also the longest in patients with Del-19+21L858R mutations, at 18.2 months. In patients with Del-19/21L858R+ atypical mutation and those with double atypical mutations, median PFS was 10.1 months and 11.1 months, respectively.
“These findings suggest that standard first-generation EGFR TKI therapy is effective in patients with Del-19+21L858R mutations, Del-19/21L858R+ atypical mutation and double atypical mutations,” said Zhang.
“The poorest response was seen in patients with complex EGFR mutations and primary drug-resistance patterns [n=20]. In these patients, the ORR was 15 percent, and median PFS was just 1.4 months,” Zhang continued.
“The prevalence of complex EGFR mutations in patients with lung adenocarcinoma was previously undocumented. Whether the presence of complex mutations would alter the efficacy of standard first-line EGFR TKI therapy had also remained unknown,” he added.