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September 2, 2021

Inserting Ensartinib Into the Starting Lineup for ALK-Rearranged Lung Cancer—A Likely Limited Role on a Deep Bench

Author Affiliations
  • 1Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston
  • 2Harvard Medical School, Boston, Massachusetts
JAMA Oncol. 2021;7(11):1615-1616. doi:10.1001/jamaoncol.2021.3369

Since the groundbreaking approval of crizotinib for the treatment of advanced ALK-rearranged (ALK-positive) non–small cell lung cancer (NSCLC) in 2011,1 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.2-5 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.6,7 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.2-5 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.

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