Neoadjuvant Osimertinib: A Step Ahead or Just a Step?
Mené sur 358 patients atteints d'un cancer du poumon non à petites cellules avec mutation EGFR et résécable, cet essai randomisé de phase III évalue l'efficacité, du point de vue de la réponse pathologique principale, et la toxicité de l'osimertinib, avec ou sans chimiothérapie, en traitement néoadjuvant
The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene in the year 2004 launched the era of personalized therapies for lung cancer1; over the past two decades, nearly a dozen molecular targets have been successfully targeted to achieve therapeutic gains for patients. Tyrosine kinase inhibitors (TKIs) with a higher selectivity to mutant receptors over the wild-type receptors confer a significant improvement in patient outcomes with relatively modest toxicity for several molecular targets in lung adenocarcinoma. Leading this list is osimertinib, which is a selective third-generation EGFR TKI, used routinely for the treatment of patients with lung adenocarcinoma whose tumor harbors the activating EGFR exon 19 deletion or exon 21 L858R point mutation. Osimertinib was the first targeted drug to be approved for the treatment of early-stage non–small cell lung cancer (NSCLC) based on the results of the ADAURA trial.2 In patients with stage IB, II, and IIIA NSCLC, administration of 3 years of osimertinib after surgical resection with or without adjuvant platinum-based chemotherapy resulted in an improvement in disease-free survival and overall survival. The 5-year overall survival rate was 88% with adjuvant osimertinib compared with 78% with placebo. A significantly lower incidence of CNS progression was observed with osimertinib. These data have resulted in the (US) Food and Drug Administration approval of osimertinib for adjuvant therapy of resected NSCLC for patients with EGFR-activating mutations.
Journal of Clinical Oncology , éditorial, 2025