Kathryn A. Gold, MD
Data from the phase III FLAURA study cemented osimertinib’s (Tagrisso) place as the frontline standard of care for patients with EGFR
-mutation positive non–small cell lung cancer (NSCLC), said Kathryn A. Gold, MD.
In FLAURA, treatment with osimertinib nearly doubled the median progression-free survival (PFS) of first-generation tyrosine kinase inhibitor (TKI) therapy with erlotinib (Tarceva) or gefitinib (Iressa). The FDA approved osimertinib in this setting in April 2018 based on these data, followed by the European Commission making the same decision in June 2018.
Preclinical data suggest that patients who progress on osimertinib and harbor a C797S resistance mutation may derive benefit from first- or second-generation agents. However, Gold explained that combination trials will be the focus of research going forward.
The space of small cell lung cancer (SCLC) varies from that of EGFR
-mutant NSCLC. Gold noted that although there have not been as many developments in SCLC as in NSCLC, the needle is beginning to move as a supplemental biologics license application for single-agent nivolumab (Opdivo) is currently under priority review by the FDA in the third-line setting.
The application is based on data from the phase I/II CheckMate-032 trial, in which single-agent nivolumab demonstrated a median overall survival (OS) of 4.4 months (95% CI, 3.0-9.3), as well as a 1-year OS rate of 33% (95% CI, 22-45) in patients with progressive SCLC following more than1 prior line of therapy.1,2
The FDA is scheduled to make its decision by August 16, 2018 under the Prescription Drug User Fee Act.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Non–Small Cell Lung Cancer, Gold, associate professor of medicine, University of California, San Diego, discussed the evolving management of EGFR
-mutant NSCLC and the latest developments in SCLC.
OncLive: Please provide an overview of your presentation.
: As we all know, EGFR
-mutant lung cancer is important to recognize clinically because these patients are treated differently. They benefit from TKIs rather than from standard chemotherapy. Until very recently, our standard treatment for patients was erlotinib, afatinib (Gilotrif), or gefitinib in the frontline setting.
More recently, the FLAURA data have been presented. That looked at patients with previously untreated EGFR
-mutant lung cancer. These patients were randomized to osimertinib versus the standard first-generation agents. The results were pretty impressive. Osimertinib clearly had improved PFS and [had] a trend toward improved overall survival [OS]. It’s also a very-well-tolerated drug. Our frontline standard of care has become osimertinib since those data were presented.
Is the future of osimertinib in combination or as a single agent?
Frontline osimertinib is here to stay for now. A 19-month PFS is pretty impressive for a very-well-tolerated drug. It’s tough to imagine frontline combinations coming in and beating [single-agent osimertinib], both in terms of tolerability and outcome.
The combinations will come in the treatment of resistance to osimertinib. We’re going to see more patients who are progressing on these drugs. Right now, we don’t have any [other] standard option for people who progress on osimertinib except for cytotoxic chemotherapy, which many of our patients would like to avoid if possible.
How has osimertinib’s approval affected sequencing for patients who progress?
It’s to be determined. Normally, if patients get erlotinib, afatinib, or gefitinib in the frontline setting and osimertinib at resistance, I don’t go back to the TKIs following progression. I tend to go straight toward chemotherapy. With osimertinib, we’re learning more about the resistance mechanisms.