Efficacy of alectinib in central nervous system metastases in crizotinib-resistant ALK-positive non–small-cell lung cancer: Comparison of RECIST 1.1 and RANO-HGG criteria
Journal
European Journal of Cancer
Journal Volume
82
Pages
27-33
Date Issued
2017
Author(s)
Gandhi L
Ignatius Ou S.-H
Shaw A.T
Barlesi F
Dingemans A.-M.C
Kim D.-W
Camidge D.R
Hughes B.G.M
de Castro J
Crino L
Léna H
Do P
Golding S
Bordogna W
Zeaiter A
Kotb A
Gadgeel S.
Abstract
Background Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase–positive (ALK+) non–small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) and Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG) criteria. Methods Both studies enrolled patients aged ?18 years who had previously received crizotinib. NP28761 was conducted in North America and NP28673 was a global study. All patients received 600 mg oral alectinib twice daily and had baseline CNS imaging. CNS response for those with baseline CNS metastases was determined by an independent review committee. Results Baseline measurable CNS disease was identified in 50 patients by RECIST and 43 by RANO-HGG. CNS objective response rate was 64.0% by RECIST (95% confidence interval [CI]: 49.2–77.1; 11 CNS complete responses [CCRs]) and 53.5% by RANO-HGG (95% CI: 37.7–68.8; eight CCRs). CNS responses were durable, with consistent estimates of median duration of 10.8 months with RECIST and 11.1 months with RANO-HGG. Of the 39 patients with measurable CNS disease by both RECIST and RANO-HGG, only three (8%) had CNS progression according to one criteria but not the other (92% concordance rate). Conclusion Alectinib demonstrated promising efficacy in the CNS for ALK+ NSCLC patients pretreated with crizotinib, regardless of the assessment criteria used. ? 2017 Elsevier Ltd
Subjects
Alectinib; CNS metastases; NSCLC; RANO-HGG; RECIST
SDGs
Other Subjects
alectinib; crizotinib; alectinib; antineoplastic agent; carbazole derivative; crizotinib; piperidine derivative; protein kinase inhibitor; pyrazole derivative; pyridine derivative; adult; aged; ALK gene; Article; central nervous system metastasis; drug efficacy; female; human; intermethod comparison; major clinical study; male; non small cell lung cancer; oncogene; outcome assessment; phase 2 clinical trial (topic); priority journal; Response Assessment in Neuro Oncology high grade glioma criteria; response evaluation criteria in solid tumors; treatment response; Carcinoma, Non-Small-Cell Lung; Central Nervous System Neoplasms; clinical trial; drug resistance; Lung Neoplasms; middle aged; pathology; phase 2 clinical trial; response evaluation criteria in solid tumors; retrospective study; secondary; young adult; Adult; Aged; Antineoplastic Agents; Carbazoles; Carcinoma, Non-Small-Cell Lung; Central Nervous System Neoplasms; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Young Adult
Publisher
Elsevier Ltd
Type
journal article