Second-line therapy with first- or second-generation tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer patients with T790M-negative or unidentified mutation.

Background: T790M mutation causes resistance to tyrosine kinase inhibitors (TKIs) in approximately 49% of patients with epidermal growth receptor-mutant non-small cell lung cancer (NSCLC). The cause of resistance in the remaining half of the cases is a minor mutation or unknown. Here, we conducted a retrospective study of epidermal growth receptor-mutant NSCLC patients with T790M-negative or an unidentified mutation to appraise the therapeutic response to first- or second-generation tyrosine kinase inhibitors as a second-line treatment.

Methods: The study included 39 patients treated in our institution from April 2012 through March 2020 with second-line tyrosine kinase inhibitors or chemotherapy after completing a first-line therapy with tyrosine kinase inhibitors.

Results: The patients were allocated to two groups: chemotherapy (n = 28) and a tyrosine kinase inhibitor (n = 11) groups. The median progression-free survival (PFS) was 5.4 months in the chemotherapy group and 3.4 months in the tyrosine kinase inhibitor group (p-value = 0.36), while the median overall survival (OS) was 16.1 months in the chemotherapy group and 12.8 months in the tyrosine kinase inhibitor group (p- value = 0.20). This study showed no significant difference in PFS and OS between the chemotherapy and tyrosine kinase inhibitor groups.

Conclusions: These observations suggest that first- and second-generation tyrosine kinase inhibitors are not recommended for second-line treatment in epidermal growth factor receptor-mutated NSCLC patients with T790M-negative mutation who have received tyrosine kinase inhibitors as first-line treatment.