Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase−Positive Non–Small Cell Lung Cancer
| Autor: | Chris Liang, V. Oertel, Ziping Wang, Yun Fan, Leora Horn, Ying Cheng, Elena Poddubskaya, Yi Zhou, Tony Mok, Li Mao, Giovanni Selvaggi, Alberto Chiappori, Irfan Cicin, Gang Wu, Heather A. Wakelee, Dae Ho Lee, Valeriy Breder, Yunpeng Liu, Jennifer G. Whisenant, Yi-Long Wu, Kim Harrow, Sergey Orlov, Martin Reck |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Adolescent medicine.drug_class Population Piperazines law.invention Crizotinib Randomized controlled trial law Carcinoma Non-Small-Cell Lung Internal medicine medicine Clinical endpoint Humans Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Lung cancer education Protein Kinase Inhibitors education.field_of_study business.industry Hazard ratio Middle Aged medicine.disease Pyridazines ALK inhibitor business medicine.drug |
| Zdroj: | JAMA Oncology. 7:1617 |
| ISSN: | 2374-2437 |
| Popis: | Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018. Eligible patients were 18 years of age or older and had advanced, recurrent, or metastatic ALK-positive NSCLC.Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily.The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary end points included systemic and intracranial response, time to central nervous system progression, and overall survival. Efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population consisting of patients with central laboratory-confirmed ALK-positive NSCLC.A total of 290 patients (149 men [51.4%]; median age, 54 years [range, 25-90 years]) were randomized. In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 [range, 0.03-44.0 months] vs 12.7 months [range, 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P .001), with a median follow-up of 23.8 months (range, 0-44 months) for the ensartinib group and 20.2 months (range, 0-38 months) for the crizotinib group. In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (95% CI, 8.9-16.6 months; hazard ratio, 0.45; 95% CI, 0.30-0.66; log-rank P .001). The intracranial response rate confirmed by a blinded independent review committee was 63.6% (7 of 11) with ensartinib vs 21.1% (4 of 19) with crizotinib for patients with target brain metastases at baseline. Progression-free survival for patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib as a result of a lower central nervous system progression rate (at 12 months: 4.2% with ensartinib vs 23.9% with crizotinib; cause-specific hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001). Frequencies of treatment-related serious adverse events (ensartinib: 11 [7.7%] vs crizotinib: 9 [6.1%]), dose reductions (ensartinib: 34 of 143 [23.8%] vs crizotinib: 29 of 146 [19.9%]), or drug discontinuations (ensartinib: 13 of 143 [9.1%] vs crizotinib: 10 of 146 [6.8%]) were similar, without any new safety signals.In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC.ClinicalTrials.gov Identifier: NCT02767804. |
| Databáze: | OpenAIRE |
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