Dr. Sequist on Rationale for TATTON Trial in EGFR-Mutant Lung Cancer

Lecia V. Sequist, MD, MPH, thoracic medical oncologist and director of the Center for Innovation in Early Cancer Detection at Massachusetts General Hospital Cancer Center, discusses the rationale for the TATTON trial in non—small cell lung cancer (NSCLC).

For the phase Ib clinical trial, investigators evaluated the use of the EGFR inhibitor osimertinib (Tagrisso) plus the MET inhibitor savolitinib in patients who had EGFR-mutant NSCLC that had developed resistance to prior EGFR-targeted therapies through MET-gene amplification.

The rationale for the study was based on findings from preclinical work which looked at MET as a resistance pathway and found that both of those components were necessary in order for the approach to be effective in this patient population. Although previous clinical trials have looked at the combination of an EGFR inhibitor and a MET inhibitor have been done in the lung cancer space, they were not conducted in a biomarker-selected population, says Sequist.

Therefore, TATTON was the first clinical trial to use the combination of 2 agents in a population that has that biomarker signature. In a cohort of 46 patients who had previously received either a first- or second-generation EGFR TKI, treatment with the combination led to an objective response rate of 52%, with 24 partial responses. The median duration of response was 7.1 months. These findings were particularly exciting, says Sequist, as they show that the concept of pairing these 2 agents can be effective when they are given to selected patients.

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