Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors in T790M-positive non-small cell lung cancer: review on emerged mechanisms of resistance

Abstract

TKIs. Here, we review principle mechanisms of innate and acquired resistance described in literature both in clinical and preclinical settings during NSCLC treatment with third-generation EGFR-TKIs.

Co‐mutational assessment of circulating tumour DNA (ctDNA) during osimertinib treatment for T790M mutant lung cancer

“…Osimertinib is an irreversible third‐generation EGFR‐TKI targeting the secondary resistant EGFR T790M mutant with outstanding clinical efficacy . Unfortunately, acquired resistance still occurs after a median of 10 months with various resistance mechanisms .…”

Monitoring EGFR TKI resistance in real time using ddPCR-based liquid biopsy: a case report

“…In this case report, it was not further investigated whether this was due to technical or biological issues/parameters, such as assay sensitivity and response to therapy or a small subset of T790M-mutated cells, respectively. ddPCR analysis did reveal the presence of MET amplification, which has already been reported as a resistance mechanism to both first-line and third-line EGFR TKI therapys 7. Interestingly, previous reports have suggested a reciprocal relationship between the EGFR T790M mutation and MET amplification.…”

Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR‐mutant non–small cell lung cancer: Multicenter, single‐arm, phase 2 trial (ABC Study)

“…The patient achieved a minor response with 6‐month PFS. Moreover, C797S (trans), human epidermal growth factor receptor 2 amplification, and minor mutations such as E709K, L718Q, and L844V have been reported as mechanisms of resistance to osimertinib, which might be sensitive to afatinib . We, therefore, speculate that afatinib‐bevacizumab combination therapy might be effective after osimertinib failure.…”