The only EGFR-tyrosine kinase inhibitor presently authorized for advanced non-small cell lung cancer (NSCLC) patients with EGFR G719X/L861Q/S768I is afatinib. However, afatinib’s advantages and resistance mechanisms in patients with these nonclassical mutations were the subjects of little real-world research. The present study was done to close the gap.

Patients with EGFR G719X/L861Q/S768I were included in the study after being screened together with all NSCLC patients who had afatinib treatment. To determine the mutant genotype, either tumor tissue or blood samples were found using commercial next-generation sequencing (NGS) panels or the amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR).

Afatinib was administered to 106 individuals with advanced NSCLC who had the mutations EGFR G719X/L861Q/S768I. Afatinib’s advantages showed variation in response to various mutation genotypes. Notably, 59 individuals had NGS testing at baseline, and TP53 was the most common comorbid mutation. Less survival advantage was observed by patients with TP53 mutations than those with TP53 wild-type. Ultimately, 68 patients progressed, and 27 patients underwent NGS analysis to identify putative resistance mechanisms. In cases, 3 (11.1%), 3 (11.1%), 3 (11.1%), 3 (11.1%), 3 (11.1%), 1 (3.7%), 1 (3.7%), and 1 (3.7%), EGFR-T790M, CDK4 amplification, FGFR1 amplification, PIK3CA, respectively. One patient was T790M-positive out of the five patients who underwent ARMS-PCR testing to look for the EGFR-T790M mutation.

The advantages of afatinib varied depending on the genotype of mutation, and the range of possible resistance mechanisms in patients with EGFR G719X/L861Q/S768I was first identified in the current study. The findings of the study could offer useful therapeutic guidance for the best therapy in the situation.