The third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib (Tagrisso) targets EGFR mutations, including T790M. Osimertinib was approved by the FDA in November 2015 for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) and the T790M mutation whose disease progressed during or after EGFR TKI therapy.
Now results from a new study indicate that osimertinib is associated with a high overall response rate and prolonged progression-free survival (PFS) in patients receiving osimertinib for the first-line treatment of EGFR mutation-positive NSCLC, according to study results presented at the 2016 European Lung Cancer Conference in Geneva, Switzerland.
“The overall response rate was among the best reported for first-line therapy of EGFR-mutated NSCLC. The progression-free survival results are exciting, well exceeding the historical control rates of 10 to 13 months with first- or second-generation drugs. Many of the patients have not had disease progression on the study and are still benefitting from treatment,” said Suresh Ramalingam, MD, Professor, Emory School of Medicine, Atlanta, GA, and study author.
The study included 60 patients with locally advanced or metastatic EGFR mutation–positive NSCLC who had participated in 2 phase 1 expansion cohorts of the AURA clinical trial. Overall, patients were randomized in a 1:1 ratio to receive osimertinib 80 mg or 160 mg daily, and the median follow-up was 16.6 months.
Impressive Response Rate in First-Line Use
The overall response rate was 77%, with a rate of 67% in patients receiving osimertinib 80 mg and 87% in patients receiving 160 mg. The median PFS was 19.3 months with osimertinib 160 mg and was not yet reached with the 80-mg dose.
The most common adverse events with both doses of osimertinib included diarrhea, stomatitis, and paronychia.
Of note, patients who did have disease progression did not have the T790M mutation as a mechanism of resistance, suggesting that “we may be changing the biology of the disease with the use of first-line osimertinib,” said Dr Ramalingam.
A phase 3 clinical trial confirmatory study will compare osimertinib and erlotinib or gefitinib for first-line treatment of patients with NSCLC.