Resistance Mechanisms Identified for NSCLC Progression With First-Line Osimertinib
The 2 most common resistance mechanisms were MET amplification, EGFR C797S mutation.
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Analysis of a subpopulation of patients from the phase 3 FLAURA study has revealed several resistance mechanisms for disease progression and/or discontinued treatment for patients administered first-line osimertinib for EGFR-mutated non-small cell lung cancer (NSCLC).1
The most commonly observed acquired resistance mechanisms in patients assigned osimertinib were MET amplification and EGFR C797S mutations, according to results presented at the 2018 ESMO Congress in Munich, Germany.
Previously presented results from the main analysis of FLAURA showed that osimertinib had superior efficacy compared with standard of care EGFR tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced NSCLC, regardless of PD-L1 expression.
Patients (556 participants) in the study were randomly assigned to receive osimertinib or an EGFR-TKI (gefitinib or erlotinib). The researchers collected paired plasma samples at baseline and at progression or treatment discontinuation, and analyzed these samples using next-generation sequencing.
Disease progression or treatment discontinuation and plasma samples were available for 41% of patients assigned to be administered osimertinib and 57% of patients were assigned to receive a TKI. Of these patients, only those with detectable EGFR mutations at baseline were evaluable (91 for osimertinib and 129 for TKIs).
In the osimertinib arm, no EGFR T790 mutations were found. Instead, MET amplification was detected in 15% of patients and EGFR C797S mutation were found in 7% of patients. Other commonly detected resistance mechanisms were HER2 amplification, PIK3CA, and RAS mutations.
In patients assigned TKIs, T790 mutations were detected in almost one-half of this population (47%). Other mechanisms that were identified included MET (4%) and HER2 gene amplification (2%).
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- Ramalingam SS. Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study. Presented at: the ESMO 2018 Congress; Munich, Germany: October 20, 2018. Abstract LBA50.