Osimertinib effectively treats epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) that has the T790M mutation, according to study findings presented at the European Lung Cancer Conference.1

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI). Although EGFR inhibition is the standard of care for patients with NSCLC that has EGFR activating mutations, approximately 50% to 60% of patients develop resistance through the T790M mutation. However, osimertinib potently inhibits the original EGFR mutations in exon 19 and exon 21 and also the T790M mutation.

This study investigated the use of osimertinib as first-line therapy for EGFR-positive NSCLC in 60 patients with locally advanced or metastatic EGFR-mutated NSCLC. Follow-up was a median of 16.6 months.

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The overall response rate was 77%. The treatment was administered in 2 doses. Progression-free survival (PFS) for patients receiving the 160-mg dose was a median of 19.3 months; median PFS had not yet been reach in patients receiving the 80-mg dose. Few adverse events occurred, particularly at the 80-mg dose; only 10% of patients required a dose reduction to manage toxicities.

“The overall response rate was among the best reported for first-line therapy of EGFR-mutated NSCLC. PFS results are exciting, well exceeding the historical control rates of 10 to 13 months with first-generation or second-generation drugs. Many of the patients have not experienced disease progression on the study and are still benefitting from treatment,” said Suresh Ramalingam, MD, professor of hematology and medical oncology at Emory School of Medicine and deputy director of Winship Cancer Institute, Atlanta, Georgia, and study author.

Initial data suggests that patients who experienced disease progression did not have T790M mutation as the mechanism of resistance. “That tells us that we may be changing the biology of the disease with the use of first-line osimertinib,” said Ramalingam.

The findings will be further investigated in a phase III clinical trial of more than 500 patients comparing osimertinib to either erlotinib or gefitinib as front-line therapy. Results are expected in up to 18 months.

A second late-breaking abstract revealed the mature results of 2 AURA studies that investigated osimertinib at the recommended 80-mg dose in patients with EGFR-mutated and T790M-positive NSCLC who had progressed on previous EGFR TKI therapy. Response rates were 71% in the phase I dose expansion cohort of 63 patients and 66% in pooled results from 2 phase II studies of 411 patients. PFS was 9.7 and 11 months for the phase I cohort and phase II studies, respectively.2

“We found a response rate and PFS that were consistent between the two studies and with earlier reports from the AURA studies,” said James Yang, MD, PhD, director of the Department of Oncology and Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan, and lead author of the study. “Adverse events such as interstitial lung disease and QT prolongation were infrequent, with similar rates to our previous analyses.”

Yang explained that this mature pooled analysis for patients with T790M-positive EGFR-mutant disease who have progressed on prior EGFR TKI treatment revealed a high overall response rate, encouraging duration of response, and a good tolerability profile. He stated that osimertinib is now standard of care for patients with EGFR mutations who have failed EGFR TKI. Finally, Yang concluded that molecular diagnosis for T790M must now be standard as well.

Osimertinib recently received accelerated approval as the first indicated treatment for patients with EGFR-T790M-mutation-positive metastatic NSCLC in the United States, Eureopean Union, and Japan.


1. Ramalingam S, Yang J, Lee C, et al. Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts. Presentation at: 2016 European Lung Cancer Conference; April 13-16, 2016; Geneva, Switzerland.

2. Yang JC, Ramalingam S, Janne P, Cantarini M, Mitusdomi T. Osimertinib (AZD9291) in pre-treated pts with T790M-positive advanced NSCLC: updated phase 1 (P1) and pooled phase 2 (P2) results. Presentation at: 2016 European Lung Cancer Conference; April 13-16, 2016; Geneva, Switzerland.