Lecia V. Sequist, MD
The combination of osimertinib (Tagrisso) and savolitinib led to early responses with no significant toxicities in patients with EGFR
-positive non–small cell lung cancer (NSCLC) who developed MET
-driven resistance, demonstrating that the regimen is efficacious in a biomarker-driven population, said Lecia V. Sequist, MD.
, Sequist highlighted the expansion cohort data from the TATTON study and explained how these findings could impact the treatment landscape of EGFR-mutant NSCLC.
OncLive: How would you define the history of EGFR-targeted therapy in EGFR-positive NSCLC?
mutations were discovered about 15 years ago; this was the first example that we had in NSCLC of testing a patient, finding a mutation, and treating them with a corresponding targeted therapy. Over the past 15 years, we acquired 5 FDA-approved EGFR TKIs. There have been many clinical trials looking to refine which ones we use and the specific indications. The current standard of care is to receive osimertinib, a third-generation EGFR TKI, as first-line treatment.
Could you expand on the role of MET amplification in resistance to EGFR therapy?
Along with the development of EGFR inhibitors, we have also expanded our understanding of what drives resistance to these drugs. Thanks to previous studies and many biopsies of patients, we have a better picture of what causes resistance. The main player—especially with the newer-generation EGFR TKIs—is MET
amplification. We know that MET
amplification can come up as a bypass pathway and cause resistance to EGFR inhibitors. From preclinical models, we know the best way to target this resistance may be to combine an EGFR inhibitor and a MET inhibitor. It looks like either drug alone would not be sufficient, but when you have a combination, you can attack this resistance pathway.
What was the rationale for this particular combination in the TATTON trial?
The TATTON clinical trial looks at patients with EGFR
-mutant NSCLC who have MET
as an acquired resistance mechanism. In this trial, investigators treated these patients with osimertinib and the MET inhibitor savolitinib. The preclinical work that looked at MET
as a resistance pathway suggested that both of those components together would be necessary in order for the treatment to be effective.
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