Dr. Liu on Resistance Mechanisms in EGFR-Mutant Lung Cancer

Stephen Liu, MD, affiliate professor of drugs, Division of Hematology and Oncology, Georgetown College Medical Heart, discusses resistance mechanisms in EGFR-mutant lung most cancers.A current examine taking a look at development on second-line osimertinib (Tagrisso) revealed that the biology of sufferers who retain T790M and those that lose T790M is basically completely different, explains Liu.Those that retain T790M appear to develop one other acquired mutation. About half of these sufferers will develop C797S. That acquired mutation prevents osimertinib from binding from the ATP cleft. Whereas, in tumors that lose T790M, sufferers develop a broad vary of various resistance mechanisms. A few of these mechanisms embrace MET amplification and mutations in PI3 kinase. These sufferers might also develop KRAS mutations, fusions in RET, BRAF, FGFR3, in addition to in ALK, NTRK, and ROS, says Liu.One other distinction lies within the time it takes to develop that resistance, says Liu. In tumors that retain T790, the time to remedy discontinuation exceeded 1 12 months. Sufferers who misplaced T790M got here off osimertinib a lot faster, suggesting that these competing mechanisms of resistance have been already current in these sufferers when T790M was detected. If physicians can detect these early on, possibly frontline remedy will be tailor-made to the affected person thereby eliminating these clones, says Liu.


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