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 non-small cell lung cancer. This should be the new standard of care for these patients,” said Nathan Pennell, MD, PhD, FASCO, ASCO Expert.

Treatment with osimertinib after surgery significantly lowered the risk of death in adults with completely resected EGFR-mutated (EGFRm) stage IB, II, or IIIA non-small cell lung cancer (NSCLC), according to the findings of an international study.

Study at a Glance

Key Findings

In this final overall survival (OS) analysis of the ADAURA study, 88% of patients with IB-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 a placebo. Overall, there was a 51% lower risk of death for those who received osimertinib compared to those who received placebo (p < 0.0001). 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 the survival benefit of osimertinib was seen regardless of whether prior adjuvant chemotherapy was received.

ADAURA is the first global phase III study to find both statistically significant disease-free-survival (DFS) – or the amount of time after treatment in which no sign of cancer is found – and statistically significant OS benefit using osimertinib in people with EGFRm stage IB-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 non-small cell lung cancer,” said Roy S. Herbst, MD, PhD, deputy director of Yale Cancer Center, assistant dean for translational research at Yale School of Medicine, and lead author of the study. “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 EGFRm stage IB-IIIA non-small-cell lung cancer. This further reinforces the need to identify these patients with available biomarkers at the time of diagnosis and before treatment begins.”

Lung cancer is the leading cause of global cancer death, accounting for almost 1.8 million deaths every year. EGFRm lung cancer represents approximately 30-40% of lung cancer cases in Asia and around 10-25% of lung cancers in the United States (U.S.) and Europe. Despite the use of chemotherapy after the removal of a tumor using surgery, disease recurrence rates in stage IB-IIIA NSCLC are high and increase with disease stage.

Osimertinib is a third-generation, central nervous system (CNS)-active EGFR-tyrosine kinase inhibitor (TKI) and is the first targeted agent to be approved by the U.S. Federal Drug Administration as an adjuvant treatment for resected stage IB-IIIA EGFRm NSCLC.

About the Study

ADAURA is a global study conducted in 26 different countries across Europe, the Asia-Pacific, North America, and South America. 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.

In total, 682 patients were randomized 1:1 to receive osimertinib (n = 339) 80 mg once daily or placebo (n = 343) until disease recurrence, treatment completion at three years, or a discontinuation criterion was met. The primary endpoint was DFS in stage II-IIIA, and key secondary endpoints were DFS in stage IB-IIIA, OS, and safety.

In data published recently, the majority of adverse events were not serious and were mild or moderate in severity, 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 for 13% (n = 43) of participants in the osimertinib group and 3% (n = 9) of participants in the placebo group.

Next Steps

Future analyses from ADAURA are underway, and they may provide more information, including tumor and circulating tumor DNA molecular profiling for minimal residual disease. Osimertinib is also currently being evaluated in other stages of NSCLC, including before surgery.