Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer A Randomized Clinical Trial

Basit Öğe Kaydı
dc.authoridWu, Yi-Long/0000-0002-3611-0258
dc.authoridLin, Fan/0000-0002-7330-3833
dc.authoridWu, Yi-Long/0000-0002-3611-0258
dc.authoridliang, YU/0009-0007-3922-3454
dc.authorwosidyu, zhang/JWO-7724-2024
dc.authorwosidliu, junyang/IXD-1201-2023
dc.authorwosidLI, Xiang-Yang/JZE-0275-2024
dc.authorwosidWu, Yi-Long/AAW-9832-2020
dc.authorwosidli, yang/IQV-3559-2023
dc.authorwosidWu, Yi-Long/GRJ-9238-2022
dc.authorwosidzhang, luyu/JJC-4227-2023
dc.contributor.authorHorn, Leora
dc.contributor.authorWang, Ziping
dc.contributor.authorWu, Gang
dc.contributor.authorPoddubskaya, Elena
dc.contributor.authorMok, Tony
dc.contributor.authorReck, Martin
dc.contributor.authorWakelee, Heather
dc.date.accessioned2024-06-12T11:18:47Z
dc.date.available2024-06-12T11:18:47Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractIMPORTANCE: 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). Objective To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.en_US
dc.description.sponsorshipXcovery Holdings Inc.en_US
dc.description.sponsorshipFinancial support for this study was provided by Xcovery Holdings Inc, which manufactures and intends to market ensartinib after approval by regulatory authorities. Xcovery Holdings Inc provided financial support for this article, including editorial and medical writing assistance by Alex Loeb, PhD, CMPP, Chrysalis Medical Communications.en_US
dc.identifier.doi10.1001/jamaoncol.2021.3523
dc.identifier.endpage1625en_US
dc.identifier.issn2374-2437
dc.identifier.issn2374-2445
dc.identifier.issue11en_US
dc.identifier.pmid34473194en_US
dc.identifier.scopus2-s2.0-85114625776en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1617en_US
dc.identifier.urihttps://doi.org/10.1001/jamaoncol.2021.3523
dc.identifier.urihttps://hdl.handle.net/20.500.14551/24962
dc.identifier.volume7en_US
dc.identifier.wosWOS:000693790600003en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Medical Assocen_US
dc.relation.ispartofJama Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEml4-Alk Fusion Geneen_US
dc.subjectInhibitoren_US
dc.subjectEfficacyen_US
dc.titleEnsartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer A Randomized Clinical Trialen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu