ESMO 2018: Resistance Mechanisms in Patients Treated with Osimertinib for Lung Cancer
Posted: Tuesday, November 13, 2018
According to preliminary data from the phase III FLAURA trial, some of the mechanisms of osimertinib resistance in patients with metastatic non–small cell lung cancer (NSCLC) have been identified. Among the heterogeneous resistance mechanisms detected with first-line osimerbinitb, MET amplification and EGFR C797S mutation were the most commonly observed. Osimertinib was previously shown to overcome the common T790M resistance mechanism. Suresh S. Ramalingam, MD, of Emory University School of Medicine, presented these late-breaking results at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich (Abstract LBA50).
This paired sample preliminary analysis evaluated acquired resistance mechanisms of a subset of patients from the study. Treatment-naive patients with locally advanced or metastatic EGFR-sensitizing mutation–positive NSCLC were randomly assigned to receive osimertinib (n = 91) or gefitinib or erlotinib (n = 129). Plasma samples were collected at baseline and after disease progression and were analyzed using next-generation sequencing.
The most commonly detected mechanisms of acquired resistance to osimertinib were MET amplification (15% of patients) and EGFR C797S (7% of patients). The most commonly detected mechanisms of resistance to standard-of-care treatment were T790M (47%), MET amplification (4%), and HER2 amplification (2%). As expected, patients treated with osimertinib did not develop resistance mechanisms due to the T790M mutation. The authors are currently investigating other novel acquired mutations in osimertinib-treated patients.
