According to findings led by researchers at Yale Cancer Center, treatment with the targeted therapy osimertinib following surgery significantly improves disease-free survival (DFS) in patients with early-stage, non-small cell lung cancer (NSCLC) with EGFR gene mutations. The benefit of osimertinib treatment demonstrated in the ADAURA trial was so substantial that the independent data monitoring committee recommended early unblinding of the multinational randomized controlled phase III trial. The findings are to be presented May 31, during the virtual Scientific Program at the annual meeting of the American Society of Clinical Oncology (ASCO).
“The disease-free survival data revealed is profound,” said Roy S. Herbst, M.D., Ph.D., Chief of Medical Oncology at YCC and Smilow Cancer Hospital, Associate Cancer Center Director for Translational Research at YCC, and co-leader of the study. “The hope was osimertinib would provide an alternative to chemotherapy for patients with early-stage lung cancer. Instead, we were thrilled to discover an incredible benefit for these patients in the fight against this deadly disease.”
The trial results showed that osimertinib offered a two-year, 89% DFS for patients with resected lung cancer (stage IB/II/IIIA) compared to a DFS rate of 53% in patients randomized to treatment with placebo, with manageable side effects. Disease-free survival measures the time from randomization to first sign of cancer recurrence or death. In this trial, patients treated with osimertinib had a 79% reduction in the risk of their cancer returning or death. The study will continue to follow patients for overall survival outcomes.
Osimertinib, an oral, daily medication, is a third-generation epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor that shuts down activity of specific genetic mutations that contribute to NSCLC in a subset of patients with the disease. In western populations about 10-15% of patients have these mutations, compared to 30-40% of lung cancer patients in Asia. Many lung cancer patients with EGFR mutations have never smoked cigarettes.
Osimertinib was first approved for use in EGFR mutation-positive advanced lung cancer in the United States in 2015 and is now approved worldwide for treament in this setting. The ADAURA clinical trial, conducted worldwide with 682 patients, is the first study of osimertinib in non-metastatic EGFR mutation-positive lung cancer.
Patients included in the clinical trial had surgery to remove their lung tumors and, in some cases, also received chemotherapy. The interim analysis showed DFS was consistent in patients using osimertinib whether or not they had prior chemotherapy.
“Osimertinib is much more specifically targeted to EGFR mutations than older generations of EGFR tyrosine kinase drugs,” said Herbst. “Therefore, it helps patients avoid recurrence of their cancer in the liver, lung, and brain.”
Herbst has followed the development of these drugs since 1997, when the first generation of the drug was developed and tested. “My career is marked by study and use of generations of EGFR inhibitor therapies, and we can now show that science and biologic medicine is making a huge impact in the earliest stages of lung cancer,” said Herbst, adding: “It’s incredible news.”
This study was funded by AstraZeneca.
Yale School of Medicine