Last November, osimertinib (Tagrisso), a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets EGFR mutations, including T790M, was approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic EGFR T790M mutation–positive non–small-cell lung cancer (NSCLC) whose disease progressed during or after EGFR TKI therapy.
In April 2016, data from a new study were presented at the 2016 European Lung Cancer Conference in Geneva, Switzerland, indicating that osimertinib is associated with a high objective response rate (ORR) and prolonged progression-free survival (PFS) in patients with NSCLC and EGFR mutation who are receiving osimertinib as first-line treatment.
“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.
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.
The overall ORR was 77%; –the ORR was 67% in patients taking 80 mg osimertinib and 87% in patients taking 160 mg osimertinib. The median progression-free survival was 19.3 months with 160 mg osimertinib, and was not yet reached with 80 mg osimertinib. The most common adverse events with both doses of osimertinib included diarrhea, stomatitis, and paronychia.
The results demonstrated that patients who had disease progression did not have T790M mutation as the 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 comparing osimertinib with erlotinib or gefitinib for the first-line treatment of NSCLC is being planned to confirm these findings.