Dr Cummings on the Investigation of Osimertinib in EGFR-Mutant NSCLC

Amy L. Cummings, MD, thoracic oncologist, assistant professor of medicine, David Geffen School of Medicine, University of California Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, discusses the significance of the phase 3 FLAURA trial (NCT02296125) evaluating osimertinib (Tagrisso) in locally advanced or metastatic non–small cell lung cancer (NSCLC).

Prior to the FLAURA trial, first-generation TKIs were the standard of care (SOC) in EGFR-mutated NSCLC, Cummings begins. The randomized, double-blind FLAURA study was designed as the first head-to-head comparison of the third-generation TKI osimertinib vs erlotinib (Tarceva) or gefitinib (Iressa) in this disease setting. The trial enrolled 556 patients who were treatment-naïve and eligible for first-line therapy, she continues. The trial’s primary end point was investigator-assessed progression-free survival (PFS), Cummings states. Key secondary end points included overall survival (OS), objective response rate, duration of response, disease control rate, depth of response, and safety.

Osimertinib was found to significantly improve PFS compared with the first-generation TKIs, Cummings says. The median PFS was 18.9 months vs 10.2 months, respectively, and the safety profile was similar across all groups.

Patients in the comparator TKI arm were allowed to cross over to receive osimertinib after they experienced progression, Cummings says, adding that the OS benefit for osimertinib was lower than expected. Patients on the osimertinib arm still demonstrated an OS of 38.6 months vs 31.8 months with the TKI. 

Additionally, a large percentage of patients in the TKI arm displayed a T790M-resistance mutation and were deemed eligible to receive subsequent osimertinib after disease progression. Despite this, only 47% of patients crossed over. This finding suggests that not all patients are able to receive second-line treatment, Cummings says. 

Overall, data from this trial support the use of osimertinib as the new SOC for advanced EGFR-mutated NSCLC.