The FLAURA study has assessed the efficacy and safety of AstraZeneca’s Osimertinib (Tagrisso) versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced non-small cell lung cancer (NSCLC). Median overall survival (OS) was improved by 6.8 months with osimertinib as a first-line treatment for patients with metastatic, EGFR-mutant NSCLC compared with erlotinib (Tarceva) or gefitinib (Iressa), despite crossover between arms, according to updated data from the Phase III study presented recently at the 2019 ESMO Congress.
The Background on Osimertinib
The FDA approved osimertinib as a frontline treatment for patients with EGFR-mutant NSCLC, based on the earlier findings from the FLAURA trial. With a trading name Tagrisso, it is a medication used to treat NSCLC with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. Developed by AstraZeneca, the medication was approved as a cancer treatment in 2017 by both the Food and Drug Administration and European Medicines Agency.
Osimertinib is used to treat locally advanced or metastatic NSCLC if the cancer cells are positive for the T790M mutation in the gene coding for EGFR. The T790M mutation may be de novo or acquired following first-line treatment with other tyrosine kinase inhibitors (TKIs), such as gefitinib and afatinib.
In the FLAURA trial, 556 treatment-naïve patients with EGFR-positive locally advanced or metastatic NSCLC were randomly assigned to osimertinib (n=279) or a standard TKI (erlotinib or gefitinib; n=277) reported Silas Inman of Targeted Oncology. Daily oral therapy was given with 80 mg of osimertinib 250 mg of gefitinib, or 150 mg of erlotinib.
Osimertinib has not only met efficacy endpoints but also had evidenced superior tolerability than the first-generation TKIs. Targeted Oncology reports that grade 3/4 adverse events (AEs) occurred in 34% of patients in the osimertinib group compared with 45% of those receiving erlotinib or gefitinib.
Investigator & Study Author Comments
Suresh S. Ramalingam, MD with the Winship Cancer Institute of Emory University and senior author reported to Targeted Oncology that “The survival results are both statistically significant and clinically meaningful with the first-line osimertinib for EGFR-mutated patients. Dr. Ramalingam continued “The overall survival result you see for the control group in this study is among the highest reported for EGFR-mutated patients. A lot of patients cross over from the control group to receive osimertinib at progression. And, even with that in play, we see a 6.8-month improvement in survival with osimertinib.
He concluded, “Osimertinib presented a favorable and consistent toxicity profile, despite prolonged exposure.”
Lead Study Author
Suresh S. Ramalingam, MD with the Winship Cancer Institute of Emory University and Senior Author