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Osimertinib Shakes Up EGFR-Mutant NSCLC Landscape

Gina Columbus @ginacolumbusonc
Published: Tuesday, May 02, 2017

Jonathan Riess, MD

Jonathan Riess, MD

Beyond the standard EGFR tyrosine kinase inhibitors gefitinib (Iressa), afatinib (Gilotrif), and erlotinib (Tarceva) for patients with EGFR-mutant non–small cell lung cancer (NSCLC), the osimertinib (Tagrisso) is also making its mark.

-mutant population.

OncLive: You spoke on EGFR-positive NSCLC. How has this field evolved?

Riess: I had the privilege to speak on EGFR-mutant NSCLC, which represents about 15% of all NSCLC. We have some special drugs—EGFR TKIs—that are very effective against treating this type of lung cancer. However, invariably, people develop progressive disease within 2 years, so new treatments and combinations are desperately needed.

mutation. I also talked about the sequencing of treatment; future directions, including potentially bringing up these third-generation drugs to frontline therapy and what that means; and how the resistance mechanisms may change and whether that would be a viable strategy in future research. 

Osimertinib just received a full FDA approval. Can you discuss its impact?

It is very exciting that this now has full approval for T790M NSCLC, which is the most common resistance mechanism to earlier-generation TKIs, so that has been a tremendous advance. However, work is needed for EGFR-mutant lung cancer that doesn’t have resistance via T790M. It has other resistance mechanisms, so we are looking at other combination therapies. Also, there are implications for if osimertinib does move up to the frontline setting with the pivotal ongoing FLAURA trial. What does that mean for the resistance mechanisms that may change; it may not be T790M, so how do we deal with that? 

What combination studies are being conducted with osimertinib? 

There is the TATTON trial that’s being led by Dr Geoff Oxnard at Dana-Farber Cancer Institute that’s looking at the various combinations including MET inhibitors, MEK inhibitors, and other drugs. We have a clinical trial at UC Davis through our UC consortium that is actually looking at osimertinib and the EGFR monoclonal antibody necitumumab in combination; that’s very exciting.
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