Treatment with osimertinib after surgery significantly lowered the risk of death in adults with completely resected EGFR-mutated stage IB, II, or IIIA non–small cell lung cancer (NSCLC), according to the findings of the international ADAURA study. The research was presented at the 2023 ASCO Annual Meeting by Roy S. Herbst, MD, PhD, and colleagues (Abstract LBA3).
EGFR-mutated lung cancer represents approximately 30% to 40% of lung cancer cases in Asia and around 10% to 25% of lung cancers in the United States and Europe. Despite the use of chemotherapy after lung cancer surgery, disease recurrence rates in patients with stage IB to IIIA NSCLC are high and increase with disease stage.
Roy S. Herbst, MD, PhD
Osimertinib is a third-generation, central nervous system–active EGFR tyrosine kinase inhibitor and is the first targeted agent to be approved by the U.S. Food and Drug Administration as an adjuvant treatment for patients with resected stage IB to IIIA EGFR-mutated NSCLC.
About the ADAURA Trial
ADAURA is a global study conducted in 26 different countries across Europe, Asia-Pacific, North America, and South America. In total, 682 patients were randomly assigned 1:1 to receive osimertinib (n = 339) at 80 mg once daily or placebo (n = 343) until disease recurrence, treatment completion at 3 years, or a discontinuation criterion was met.
Approximately two-thirds of patients in the study were women. Patients were aged between 30 and 86 years, with an average age of 64 years in the osimertinib group and 62 years in the placebo group. Approximately two-thirds of patients had no history of smoking, and approximately two-thirds of patients were Asian.
The primary endpoint was disease-free survival in patients with stage II to IIIA disease, and key secondary endpoints were disease-free survival in stage IB to IIIA disease, overall survival, and safety.
Key Findings
In this final overall survival analysis of the ADAURA study, 88% of patients with IB to IIIA NSCLC who were given osimertinib following the removal of their tumor were still alive 5 years after surgery, compared to 78% of patients treated with placebo. Overall, there was a 51% lower risk of death for those who received osimertinib compared to those who received placebo (P < .0001).
This survival benefit with adjuvant osimertinib was observed consistently in an exploratory analysis across all study subgroups, including in those with stage IB, II, and IIIA NSCLC. Adjuvant chemotherapy had been given to 60% of study participants before assignment to the study’s treatment groups, and a survival benefit with osimertinib was seen regardless of whether prior adjuvant chemotherapy was received.
The majority of adverse events mild or moderate, and overall rates of dose reductions and treatment discontinuation were as expected based on existing data for osimertinib. Overall, 66% (n = 222) of participants in the osimertinib group and 41% (n = 139) of participants in the placebo group completed the planned treatment duration of 3 years. Adverse events led to treatment discontinuation in 13% (n = 43) of participants in the osimertinib group and 3% (n = 9) of participants in the placebo group.
ADAURA is the first global phase III study to find both statistically significant disease-free-survival and statistically significant overall survival benefit using osimertinib in patients with EGFR-mutated stage IB to IIIA NSCLC.
“Overall survival has historically been considered the gold standard efficacy endpoint for randomized adjuvant clinical trials. The results of the ADAURA trial will broaden treatment access for patients with EGFR-mutated NSCLC,” said lead study author Dr. Herbst, Deputy Director of Yale Cancer Center, Assistant Dean for Translational Research at Yale School of Medicine. “Together with the practice-changing disease-free survival data from our primary analysis, the overall survival benefit instills confidence that adjuvant osimertinib is the standard of care for patients with resected EGFR-mutated stage IB to IIIA NSCLC. This further reinforces the need to identify these patients with available biomarkers at the time of diagnosis and before treatment begins.”
Next Steps
Future analyses from ADAURA are underway, and they may provide more information, including tumor and circulating tumor DNA molecular profiling for measurable residual disease. Osimertinib is also currently being evaluated in patients with other stages of NSCLC, including as well as neoadjuvantly.
ASCO Perspective
“We have been using one-size-fits-all adjuvant chemotherapy for every patient with lung cancer despite a decade of advances in targeted treatments for select groups of patients that result in dramatically better outcomes. In a first for the lung cancer field, adjuvant osimertinib unequivocally improves survival in people with resected EGFR-mutated NSCLC. This should be the new standard of care for these patients,” said ASCO expert Nathan Pennell, MD, PhD, FASCO.
Disclosure: This study was funded by AstraZeneca. For full disclosures of the study authors, visit coi.asco.org.
