Lecia V. Sequist, MD, MPH
2017 marked a year of highlights across the non–small cell lung cancer (NSCLC) field, with clinical advancements in both targeted therapies and immunotherapy. Focusing on EGFR
-positive patients, the treatment paradigm seemingly transformed overnight with the release of the phase III FLAURA findings.
The trial, which compared osimertinib (Tagrisso), a third-generation EGFR tyrosine kinase inhibitor (TKI), with standard first-generation EGFR TKIs erlotinib (Tarceva) or gefitinib (Iressa), demonstrated a statistically significant improvement in progression-free survival (PFS) with osimertinib in treatment-naïve EGFR
-positive NSCLC patients.
Now the agent, which is currently approved in the second-line setting for patients who harbor the T790M resistance mutation, has been granted an FDA priority review for a first-line indication. With this news, experts are debating whether it will be more effective to administer osimertinib or standard agents first, especially since resistance mechanisms that may develop from osimertinib treatment remain unknown.
In addition, combination regimens could be the next step for osimertinib, since its safety profile is more manageable than first- and second-generation agents.
Lecia V. Sequist, MD, associate professor of medicine at Harvard Medical School, the Mary B. Saltonstall Endowed Chair in Oncology at Massachusetts General Hospital, lectured on sequencing with EGFR
-targeted agents in NSCLC at the 2017 OncLive®
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer.
In an interview during the meeting, she reflected on the practice-changing osimertinib data, ongoing trials exploring combination regimens, and the hope that there might still be potential for immunotherapy in this patient subgroup.
OncLive: You spoke on targeted therapies and EGFR sequencing. What are some key things to note in this space?
We saw some exciting data this year when it comes to EGFR
-positive NSCLC with the FLAURA study, which was just recently presented at the 2017 ESMO Congress. In this randomized trial, they were looking at the third-generation T790M inhibitor osimertinib, which is usually given in the second-line setting after acquired resistance. In this trial, they were moving it up to the frontline setting and comparing it with standard of care—either erlotinib or gefitinib—and the trial showed that osimertinib has a much longer—almost double—median PFS, which was quite significant. In addition, this drug also has a much more tolerable safety profile.