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Multicenter Analysis of Mechanisms of Resistance to Osimertinib in EGFR Mutated NSCLC: An ATOMIC Registry Study

*January 2021*

The ATOMIC consortium is a group of thoracic oncologists from North America. They received funding from AstraZeneca to build a registry of patients with EGFR+ NSCLC. The registry contains all treatments given, molecular tests performed, and radiologic results.The registry contains data on 1187 patients with EGFR+ NSCLC. This analysis is focused on the 799 patients that received osimertinib, but there is clearly the opportunity to mine this database in the future to learn more about this deadly disease.

We looked at the 163 patients for whom we had NGS data after osimertinib. We found that T790 loss was a common molecular change, and this happened mostly after osimertinib treatment. In contrast, EGFR amplification and CDKN2A/B loss often preceded and followed osimertinib.

How did changes compare between tissue and liquid testing? Consistent with prior work, we see that liquid and tissue testing had pretty similar results in terms of mechanisms of resistance seen, though amplification was called more often on plasma. Mechanisms of resistance seen for 1st line osimertinib vs 2nd line osimertinib: T790 loss was much more common with 2nd line  (with 1st line: T790 likely won’t develop). Interestingly, gene rearrangements were also only seen with 2nd line osimertinib.

Where are we going next with this project? We are going through the registry right now to annotate each molecular alteration to determine which alterations are more likely to be clinically relevant. We are also working to incorporate results from PCR, FISH and IHC testing that was done, as well as histologic transformations. We are hopeful that this registry will prove a rich source of data to better understand this disease..Read more and see charts.