Authors: Ana Ortega-Franco & Shereen Rafee
Abstract
The introduction of tyrosine kinase inhibitors (TKI) for the treatment of metastatic non-small cell lung cancer (NSCLC) harbouring sensitizing epidermal growth factor receptor (EGFR) gene mutations revolutionized the diagnostic and treatment algorithm of this subset of patients almost two decades ago. Since then, a number of trials have evaluated the role of TKI therapy in early-stage disease, with encouraging disease-free survival (DFS) results but lack of a survival advantage. ADAURA, a phase III trial evaluating 3 years of adjuvant osimertinib versus placebo in patients harbouring EGFR mutations with completely resected stage IB–IIIA NSCLC, recently reported a profound DFS benefit (hazard ratio 0.21), favourable quality of life and reduction in the risk of brain metastases. These results led to osimertinib’s fast track approval by the US Food and Drug Administration, with this drug thus becoming the first EGFR-TKI approved for the treatment of early-stage disease. However, the key endpoint of overall survival remains immature and questions around indication (i.e. stage, need for adjuvant chemotherapy), optimal treatment duration, biomarkers of response and cost-effectiveness remain to be answered. In this article, we critically appraise the findings of ADAURA and discuss future challenges.
Key Summary Points |
Osimertinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved by the US Food and Drug Administration for the treatment of completely resected stage IB-IIIA EGFR-mutant non-small cell lung cancer, with the fast-track approval based on the results of the ADAURA trial which showed an unprecedented disease-free survival benefit. |
However, survival data is largely immature. With prior evidence suggesting that adjuvant EGFR-TKIs prolong disease-free survival (DFS) but not survival, the question is whether we can now rely on DFS to adopt adjuvant osimertinib in the clinic. |
Findings from ADAURA also allow reflection on other relevant topics of this field, such as optimal treatment indication and sequence, biomarkers for response, patterns of relapse, quality of life and cost-effectiveness. |