Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase−Positive Non–Small Cell Lung Cancer

• DOI: 10.1001/jamaoncol.2021.3523
• Publication Date: 2021-09-02T16:03:48Z
• Authors: Leora Horn; Ziping Wang; Gang Wu; Elena Poddubskaya; Tony Mok; Martin Reck; Heather Wakelee; Alberto A. Chiappori; Dae Ho Lee; Valeriy Breder; Sergey Orlov; Irfan Cicin; Ying Cheng; Yunpeng Liu; Yun Fan; Jennifer G. Whise...; Yi Zhou; Vance Oertel; Kim Harrow; Chris Liang; Li Mao; Giovanni Selvaggi; Yi-Long Wu
• Keywords: ALK inhibitor; Clinical endpoint; Ceritinib; Progression-free survival

Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).To compare ensartinib crizotinib among advanced NSCLC who had not received prior treatment ALK inhibitor.This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers 21 countries enrolled 290 between July 25, 2016, November 12, 2018. Eligible were 18 years age or older advanced, recurrent, metastatic NSCLC.Patients randomized (1:1) to ensartinib, 225 mg once daily, crizotinib, 250 twice daily.The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary points included intracranial response, time progression, overall survival. Efficacy evaluated the intent-to-treat (ITT) population as well a prespecified modified ITT (mITT) consisting laboratory-confirmed NSCLC.A total (149 men [51.4%]; median age, 54 [range, 25-90 years]) randomized. In population, PFS significantly longer than (25.8 0.03-44.0 months] vs 12.7 months 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P < .001), follow-up 23.8 (range, 0-44 months) group 20.2 0-38 group. mITT reached, (95% 8.9-16.6 months; 0.45; 95% 0.30-0.66; .001). The response rate confirmed by committee 63.6% (7 11) 21.1% (4 19) target brain metastases at baseline. Progression-free without reached 16.6 result lower progression (at 12 months: 4.2% 23.9% crizotinib; cause-specific 0.32; 0.16-0.63; = Frequencies treatment-related serious adverse events (ensartinib: 11 [7.7%] crizotinib: 9 [6.1%]), dose reductions 34 143 [23.8%] 29 146 [19.9%]), drug discontinuations 13 [9.1%] 10 [6.8%]) similar, any new safety signals.In this clinical trial, showed superior both disease. Ensartinib represents first-line option NSCLC.ClinicalTrials.gov Identifier: NCT02767804.