Inserting Ensartinib Into the Starting Lineup for ALK-Rearranged Lung Cancer—A Likely Limited Role on a Deep Bench
Mené dans 21 pays sur 290 patients atteints d'un cancer du poumon non à petites cellules ALK+ de stade avancé (âge médian : 54 ans), cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ensartinib et du crizotinib (durée médiane de suivi : 23,8 mois)
Since the groundbreaking approval of crizotinib for the treatment of advanced ALK-rearranged (ALK-positive) non–small cell lung cancer (NSCLC) in 2011, the therapeutic landscape for this disease has evolved at a staggering pace. Indeed, the past decade has witnessed US Food and Drug Administration approvals of 4 additional ALK tyrosine kinase inhibitors (TKIs): ceritinib, alectinib, brigatinib, and lorlatinib. These next-generation ALK TKIs represent a significant advance compared with the first-generation ALK TKI crizotinib in terms of central nervous system penetration and overall potency. Although these promising characteristics initially positioned next-generation ALK TKIs as salvage therapies for crizotinib-resistant tumors, these drugs have since leapfrogged crizotinib and emerged as the preferred first-line option based on findings from multiple phase 3 studies. The tremendous successes of drug development for ALK-positive NSCLC and the rapid translation of these advances into significant survival gains have definitively established management of ALK-positive NSCLC as a model of precision medicine while also raising questions regarding ways to maximize benefit from the expanding repertoire of viable therapies.
JAMA Oncology , éditorial, 2020