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David S. Ettinger, MD, FACP, FCCP


Molecular Profiling of Patients With Progressive NSCLC After Osimertinib Treatment

By: Cordi Craig, MS
Posted: Monday, October 10, 2022

Although the third-generation EGFR tyrosine kinase inhibitor osimertinib is a preferred first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC), many patients may eventually develop progressive disease. Results of the ELIOS trial, presented during the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA53), compared the patient tumor tissue biopsies from baseline and after the development of progressive disease who received osimertinib to evaluate resistance mechanisms. Zofia Piotrowska, MD, MHS, of Massachusetts General Hospital, Boston, and colleagues, reported that the safety and efficacy outcomes of the ELIOS trial were consistent with the FLAURA trial.

The study authors enrolled 154 patients with EGFR tyrosine kinase inhibitor–naive advanced NSCLC with a related sensitizing mutation who were treated with osimertinib. The patients had tumor biopsies before and after the development of progressive disease. Samples were analyzed with next-generation sequencing. The median age of patients was 62, and 77% of patients identified as Asian. The exon 19 deletion, L858R, and atypical EGFR mutations were reported in 55%, 38%, and 7% of the patient population, respectively.

At data cutoff, 119 patients had progressive disease. Of those patients, 46 (39%) had evaluable paired biopsies. The median progression-free survival was 16.4 months. Consistent with previous data, MET amplification was the main acquired resistance mechanism to osimertinib. The study authors identified NKX2.1 amplification as a potential new resistance marker. Overall, 97% of patients reported adverse events, and 31% reported serious adverse events.

“Paired biopsies were obtained in only 39% of patients, highlighting the challenges of obtaining postprogressive disease tissue biopsies and the need for more comprehensive noninvasive testing methods,” the study authors concluded.

Disclosure: For full disclosures of the study authors, visit

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