Thomas J. Lynch, MD, director, Yale Cancer Center, physician-in-chief, Smilow Cancer Hospital at Yale-New Haven, Giant of Lung Cancer Care, explains how resistance occurs when treating patients with lung cancer using EGFR TKIs.
Lynch says that while EGFR TKIs help patients with EGFR
-mutated lung cancer, the vast majority of these patients will develop resistance. Half of the time, resistance is caused by the T790M
mutation, Lynch says. The other instances of resistance are caused by other factors, such as amplification of the MET
gene, mutations in the PI3K
gene, or mutations or amplification of the HER2
This variation in the resistance mechanism warrants rebiopsy for patient who develop resistance to frontline therapy, Lynch notes. Biopsying a patient after resistance can help physicians decide which agent to give their patient next. Novel next-generation EGFR inhibitors are being developed that are targeted against the T790M
acquired mutation. These therapies, AZD9291 and rociletinib (CO-1686), have demonstrated response rates near 60% in clinical trials.
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