Alectinib in Crizotinib-Refractory ALK-Rearranged Non–Small-Cell Lung Cancer: A Phase II Global Study
Top Cited Papers
- 1 March 2016
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 34 (7), 661-668
- https://doi.org/10.1200/jco.2015.63.9443
Abstract
PurposeCrizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC.Patients and MethodsAlectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC).ResultsOf the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5....This publication has 24 references indexed in Scilit:
- FDA Approval: Ceritinib for the Treatment of Metastatic Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung CancerClinical Cancer Research, 2015
- Alectinib Shows Potent Antitumor Activity againstRET-Rearranged Non–Small Cell Lung CancerMolecular Cancer Therapeutics, 2014
- Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastasesCancer Chemotherapy and Pharmacology, 2014
- Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistanceCancer Letters, 2014
- Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLCAnnals of Oncology, 2014
- Crizotinib versus Chemotherapy in AdvancedALK-Positive Lung CancerThe New England Journal of Medicine, 2013
- Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 studyThe Lancet Oncology, 2012
- Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802)Bioorganic & Medicinal Chemistry, 2012
- CH5424802, a Selective ALK Inhibitor Capable of Blocking the Resistant Gatekeeper MutantCancer Cell, 2011
- Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung CancerThe New England Journal of Medicine, 2010