Roy S. Herbst, MD, PhD

FORMAL STUDY discussant, Roy S. Herbst, MD, PhD, Chief of Medical Oncology at the Yale Cancer Center, New Haven, Connecticut, stated that the findings of the TATTON analyses are “compelling,” and the combination of osimertinib plus savolitinib can be considered a “win,” although randomized trials are needed.

“We have come a long way in the treatment of EGFR-mutated non–small cell lung cancer [NSCLC],” commented Dr. Herbst. “There are other potentially actionable mutations in NSCLC, including MET, which could be present in up to 30% of patients. All patients are tested for EGFR, and we have a number of good EGFR tyrosine kinase inhibitors for NSCLC, but cure is not possible because undoubtedly resistance will occur.”

“If resistance is due to the EGFR T790M mutation, osimertinib is designed to attack that. If EGFR T790M is not involved, patients go back to chemotherapy. MET resistance is a new and important target, found in about 15% of patients,” he continued. “The data from TATTON are exciting and represent an unmet need.”

Clinical Implications

“IT IS GREAT to see MET making it in clinical practice. In TATTON, the investigators used all three methods of testing for MET amplification. The toxicity looks better with osimertinib plus savolitinib than with osimertinib and selumetinib. It may be that the dose of savolitinib can be reduced,” Dr. Herbst said.

“The study suggests that the last line of therapy might not be the best use of this combination. Front-line trials might be warranted,” he added.

“For MET-positive patients, TATTON provides impressive early data. We need randomized trials to establish the role of this combination. We need to determine the best assay for MET amplification and to better define MET selection criteria,” Dr. Herbst noted. ■

DISCLOSURE: Dr. Herbst is a consultant for AbbVie Pharmaceuticals, Armo Biosciences, AstraZeneca, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serrano, Genentech/ Roche, Genmab, Halozyme, Heat Biologics, Infinity Pharmaceuticals, Loxo Oncology, Merck, Nektar, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Tesaro, and Tocagen; has received research support from AstraZeneca, Eli Lilly, and Merck; and is a member of the Board of Directors (nonexecutive/independent) for Junshi Pharmaceuticals.