“The improvement in disease-free survival following surgery that was seen in the ADAURA study supports the use of this targeted therapy in an earlier stage of disease,” said ASCO chief medical officer and executive vice president Dr. Richard L. Schilsky.
Treatment with Tagrisso (osimertinib) following surgery is the first targeted agent in a global randomized trial to demonstrate statistically significant improvement of disease-free survival (DFS) in patients with stage 2-3A EGFR mutation-positive non-small cell lung cancer (NSCLC), according to results from the ADAURA trial presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.
The risk of disease recurrence or death was reduced by 83% for patients with stage 2-3A disease treated with Tagrisso compared to placebo. There was also a consistent improvement of DFS, the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms, regardless of whether patients received adjuvant chemotherapy prior to enrollment.
“While osimertinib is already a standard of care for front-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer, the improvement in disease-free survival following surgery that was seen in the ADAURA study supports the use of this targeted therapy in an earlier stage of disease,” said ASCO chief medical officer and executive vice president Dr. Richard L. Schilsky.
The data showed DFS at two years was 90% for patients receiving study drug compared to 44% for those receiving placebo among patients with stage 2-3A NSCLC with an EGFR mutation. In the overall population (stage 1B-3A), DFS at two years was 89% for the Tagrisso group compared to 53% for the placebo group.
Even more, the overall population saw a 79% reduction in the risk of disease recurrence when treated with Tagrisso compared to placebo.
The trial consisted of 682 patients with primary non-squamous stage 1B-3A NSCLC and confirmed EGFR mutation. The patient population was randomized to receive either adjuvant Tagrisso (n = 339) or placebo (n = 343) for up to three years. The study drug was administered to patients once daily via an 80 mg tablet.
In total, 31% in each group had stage 1B disease and 69% had stage 2/3A disease. A larger portion of both groups were female, with 68% in the study drug group and 72% in the placebo group.
The researchers chose a third-generation drug and placebo over first- or second-generation options — which showed no statistically significant impact on DFS in previous studies – to maximize positive effects through a longer time period so that the drug can safely be taken by patients.
“The feeling was that [first- and second-generation] drugs couldn’t be given for three years,” said lead study author Dr. Roy S. Herbst. “The ideal is to give the drug longer to hopefully have a much more profound effect on outcome. I think what we’ve shown in this trial is that we can give the [third generation] drug for longer periods of time.”
DFS in stage2/3A patients was the primary outcome in the study. Other secondary endpoints included DFS in the overall population; DFS at two, three, four, and five years; overall survival; safety; and quality of life.
Lung cancer accounts for more than 1.7 million deaths annually, making it the leading cause of cancer death globally. More specifically, NSCLC constitutes 85% of all lung cancer cases, with 30% of patients presenting with resectable disease at diagnosis.
Herbst, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital, explained that future studies are in the works regarding the DNA of patients drawn at regular intervals during the ADAURA trial to combat patients developing a resistance to these agents. More, neoadjuvant therapy is being examined to eventually “move the best drugs, the most targeted drugs, as early as possible in the disease.”
These results, according to the researchers, demonstrate that adjuvant Tagrisso provides a highly effective treatment for patients after complete tumor resection and is a viable alternative front-line therapy for localized NSCLC with EGFR mutation.