Dr. Sequist Distinguishes Osimertinib From Earlier NSCLC TKIs

Lecia V. Sequist, MD, associate professor of medicine, Harvard Medical School, Mary B. Saltonstall Chair, Oncology, Massachusetts General Hospital Center, discusses the tolerability of a new third-generation T790-specific inhibitor, osimertinib (Tagrisso).

Promising data from the FLAURA study, presented at the 2017 ESMO Congress, detailed a randomized trial looking at a new third-generation T790-specific inhibitor called osimertinib. Though this drug is typically given in the second-line setting after acquired resistance, the trial tested its efficacy in the frontline setting. It was also compared with standard regimens of erlotinib (Tarceva) or gefitinib (Iressa). Results showed the drug had almost double the median progression-free survival (PFS), suggesting a much more tolerable safety profile.

The difference between osimertinib and other third-generation drugs not yet approved is in their EGFR wild-type activity level. Third-generation drugs have very little activity against EGFR wild-type, whereas first- and second-generation drugs have some degree of inhibition of EGFR wild-type. The inhibition of that wild-type is responsible for rashes and diarrhea in patients. Osimertinib has much less rash and diarrhea and greater tolerability in patients, Sequist confirms.