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ctDNA Clearance and Savolitinib Plus Osimertinib in MET-Amplified Lung Cancer

By: Susan Reckling
Posted: Monday, August 3, 2020

Geoffrey Oxnard, MD, of Dana-Farber Cancer Institute, Boston, and colleagues took a close look at circulating tumor DNA (ctDNA) clearance at two doses of the oral MET tyrosine kinase inhibitor (TKI) savolitinib and one dose of the oral third-generation TKI osimertinib in patients with EGFR mutation–positive, MET-amplified non–small cell lung cancer (NSCLC). Based on analysis of Parts B and D of the phase Ib TATTON trial, the investigators reported that ctDNA clearance appeared to correlate with longer progression-free survival. In fact, cycle 3 day 1/cycle 4 day 1 were found to be the optimal time points for predicting progression-free survival. Their results were presented during the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II (Abstract CT303).

“ctDNA clearance was similar between the two doses of savolitinib [600 mg and 300 mg daily], suggesting efficacy is maintained at the lower dose,” Dr. Oxnard and colleagues noted.

In this next-generation sequencing-based analysis, ctDNA samples were collected predose, at cycle 1 day 1, and at least every 3 to 8 weeks until treatment discontinuation. A total of 107 patients from Part B received 80 mg of osimertinib and 600 mg of savolitinib daily and 42 patients from Part D who also received 80 mg of osimertinib but 300 mg of savolitinib daily. Of these patients, evaluable ctDNA clearance data were from 49 patients from Part B and 20 patients from Part D.

A correlation between ctDNA clearance and longer progression-free survival was reported. In addition, cycle 3 day 1/cycle 4 day 1 were identified as the optimal time points for predicting progression-free survival. ctDNA clearance was comparable at these time points for patients in both Parts B and D who had received no prior EGFR TKI.



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