Jonathan W. Goldman, MD, discusses the use of osimertinib in the first line setting for patients with non–small cell lung cancer.
Jonathan W. Goldman, MD, associate professor of medicine in the hematology/oncology division, director of clinical trials in thoracic oncology, and the associate director of early drug development at UCLA Health, discusses the use of osimertinib (Tagrisso) in the first-line setting for patients with non–small cell lung cancer (NSCLC) whose disease harbors an EGFR mutation.
Results from the FLAURA trial (NCT02296125) showed that the EGFR inhibitor was superior to EGFR tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva) and gefitinib (Iressa) with a median progression-free survival of 18.9 months compared with 10.2 months in the osimertinib and standard TKI arms, respectively (HR 0.46; 95% CI, 0.37-0.57, P < .001).
At the time of the initial study, overall survival (OS) data were immature but after 2 years the researchers found a median OS of 38.6 months (95% CI, 34.5-41.8) for patients given osimertinib vs 31.8 months (95% CI, 26.6-36.0) for those given the standard TKIs (HR 0.80; 95.05% CI, 0.64-1.00, P = .046).
These results helped bolster the use of osimertinib as a frontline treatment for untreated patients with EGFR mutated advanced NSCLC ahead of combination therapy and other TKIs. However, Goldman discusses the ongoing FLAURA2 trial (NCT04035486) looking at the use of osimertinib and chemotherapy together in the frontline setting to treat patients with NSCLC. Further, he discusses some of the challenges with osimertinib in this setting and at what point physicians should consider second-line therapy.
0:08 | For our EGFR-[mutated] patients, we're frequently going to osimertinib as a first-line [therapy]. There are some circumstances where we look at other agents in combination, but that would be rare. There is another ongoing first-line trial that's called FLAURA2 that is asking the question, if we start patients on osimertinib with chemotherapy, do they do better than osimertinib alone? And we don't have the results for that. So, at this point, that would not be a standard-of-care recommendation.
0:41 | The challenge comes that osimertinib, for an average patient, works just over a year and a half. There are some [patients] with more aggressive specifics to their tumor where it might be closer to a year, but there are others as well that on the other side might get 2, 3, or more years. One of the nice facts from the FLAURA trial that we talked about is that over a quarter of the patients were still on osimertinib beyond 3 years. It's not that rare that we see these long-term benefits, but most patients will at some point develop resistance and then we have to look at a next-line therapy.