Phase II study of crizotinib in east asian patients with ROS1-positive advanced non–small-cell lung cancer
Journal
Journal of Clinical Oncology
Journal Volume
36
Journal Issue
14
Pages
1405-1411
Date Issued
2018
Author(s)
Wu Y.-L
Kim D.-W
Lu S
Zhou J
Seto T
Yang J.-J
Yamamoto N
Ahn M.-J
Takahashi T
Yamanaka T
Kemner A
Roychowdhury D
Paolini J
Usari T
Wilner K.D
Goto K.
Abstract
Purpose Approximately 1% to 2% of non–small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 (ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1–defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95% CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95% CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports. ? 2018 by American Society of Clinical Oncology.
SDGs
Other Subjects
crizotinib; protein; ros1 protein; unclassified drug; crizotinib; oncoprotein; protein kinase inhibitor; protein tyrosine kinase; ROS1 protein, human; adult; advanced cancer; aged; antineoplastic activity; bradycardia; cancer growth; cancer patient; cohort analysis; Conference Paper; constipation; decreased appetite; diarrhea; drug efficacy; drug safety; dysgeusia; East Asian; edema; fatigue; female; gene; human; human tissue; hypertension; hypertransaminasemia; leukopenia; major clinical study; male; nausea; neutropenia; non small cell lung cancer; open study; phase 2 clinical trial; priority journal; progression free survival; prospective study; response evaluation criteria in solid tumors; ros1 gene; systemic therapy; visual disorder; vomiting; China; clinical trial; ethnology; fluorescence in situ hybridization; gene rearrangement; genetics; Japan; Kaplan Meier method; lung tumor; middle aged; multicenter study; non small cell lung cancer; oral drug administration; pathology; South Korea; Taiwan; treatment outcome; Administration, Oral; Aged; Carcinoma, Non-Small-Cell Lung; China; Crizotinib; Female; Gene Rearrangement; Humans; In Situ Hybridization, Fluorescence; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Republic of Korea; Taiwan; Treatment Outcome
Publisher
American Society of Clinical Oncology
Type
conference paper