Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is efficacious for the first-line treatment of patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), a late-breaking study presented at the European Lung Cancer Conference (ELCC) 2016 has shown.1

Although EGFR inhibitors are the standard of care for patients with NSCLC who harbor EGFR-activating mutations, nearly 50% to 60% of patients develop a resistance-inducing T790M mutation. Because osimertinib is a potent inhibitor of EGFR exon 19 and exon 21 mutations, as well as the T790M mutation, researchers sought to evaluate the efficacy of osimertinib as first-line therapy in this patient population.

For the expansion portion of the phase 1 AURA trial, researchers enrolled 60 patients with locally advanced or metastatic EGFR-mutant NSCLC. Of those, 5 patients tested positive for the T790M mutation at study entry. Half of the participants received osimertinib 80 mg orally daily and the other half received the TKI at a dose of 160 mg/day.

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Results showed that at a median follow-up of 16.6 months, the overall response rate was 77% (95% CI, 64 – 87). Specifically, the overall response rate was 67% (95% CI, 47 – 83) in the 80 mg group and 87% (95% CI, 69 – 96) in the 160 mg cohort. Median duration of response for the overall study population has not yet been reached (95% CI, 12.5 – not calculable).

“The overall response rate was among the best reported for first-line therapy of EGFR mutated NSCLC,” said lead author Suresh Ramalingam, MD, professor of hematology and medical oncology at Emory School of Medicine and deputy director of Winship Cancer Institute in Atlanta, GA.

Researchers also found that median progression-free survival was 19.3 months (95% CI, 13.7 – not calculable) overall. Median progression-free survival had not yet been reached in the 80 mg cohort (95% CI, 12.3 – not calculable) and was 19.3 months (95% CI, 11.1 – 19.3) in the 160 mg arm. The 18-month progression-free survival rate was 55% overall, 57% in the 80 mg cohort, and 53% in the 160 mg cohort. The disease control rate was 97% overall (95% CI, 88.5 – 99.6).

“The progression-free survival results are exciting, well exceeding the historical control rates of 10 to 13 months with first- or second-generation drugs,” Dr Ramalingam said. “Many of the patients have not had disease progression on the study and are still benefitting from treatment.”

Initial results further demonstrated 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,” Dr Ramalingam noted.

In terms of safety, 10% and 47% of patients in the 80 mg and 160 mg cohorts, respectively, required dose reduction to manage treatment-related adverse events. The most frequently reported grade 3 or worse adverse events were diarrhea, stomatitis, and paronychia.

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The findings of this study will be further investigated in a phase 3 trial that will compare osimertinib to either erlotinib or gefitinib for first-line treatment in 500 patients. Results of that trial are expected in up to 18 months.

Osimertinib is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC under accelerated approval based on tumor response rate and duration of response by the U.S. Food and Drug Administration. It is approved at dose of 80 mg once daily.


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