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Rebiopsying 155 patients whose targeted pill had stopped working put numbers on how they escape: about two thirds by one mutation, a few by making extra copies of another receptor, and a few by turning into a different kind of cancer altogether.
Patients with lung adenocarcinoma and acquired resistance to erlotinib or gefitinib enrolled in a prospective biopsy protocol and underwent rebiopsy after resistance developed. Histology was reviewed and samples genotyped for mutations in EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS and PIK3CA, with fluorescence in situ hybridisation for MET and HER2. Adequate samples were obtained in 155 patients. Ninety-eight had a second-site EGFR T790M mutation, 63%, and four had small-cell transformation, 3%. MET amplification was seen in 4 of 75, 5%, and HER2 amplification in 3 of 24, 13%. No acquired mutations were detected in PIK3CA, AKT1, BRAF, ERBB2, KRAS, MEK1 or NRAS among 88 tested. Overlap between mechanisms was seen in 4%.
It is the reference frequency table for resistance to first-generation EGFR inhibitors, and it made rebiopsy at progression standard rather than exceptional, because the mechanism decides the next treatment and cannot be guessed.
Shares MET amplification (gene copy number), EGFR T790M, MET amplification (bypass resistance), Histologic transformation.
Shares MET amplification (gene copy number), MET amplification (bypass resistance), Gefitinib, Erlotinib.
Shares EGFR T790M, Gefitinib, Erlotinib, Resistance routes: how a blocked pathway comes back.
Shares EGFR T790M, Histologic transformation, Lineage plasticity & neuroendocrine transformation, Resistance routes: how a blocked pathway comes back.
Shares Histologic transformation, Lineage plasticity & neuroendocrine transformation, Resistance routes: how a blocked pathway comes back, Drug resistance (primary and acquired).
Shares EGFR T790M, Biopsy, Resistance routes: how a blocked pathway comes back, MET.
Shares Biopsy, Clinical Cancer Research, MET, Receptor tyrosine kinase activation.
Shares EGFR T790M, Resistance routes: how a blocked pathway comes back, Drug resistance (primary and acquired), Receptor tyrosine kinase activation.