Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non–Small-Cell Lung Cancer

• DOI: 10.1200/jco.2017.75.5587
• Publication Date: 2018-03-29T19:59:21Z
• Authors: Yi-Long Wu; James Chih-Hsin Yang; Dong-Wan Kim; Shun Lu; Jianying Zhou; Takashi Seto; Jin-Ji Yang; Noboru Yamamoto; Myung-Ju Ahn; Toshiaki Takahashi; Takeharu Yamanaka; Allison Kemner; Debasish Roychowd...; Jolanda Paolini; Tiziana Usari; Keith D. Wilner; Koichi Goto
• Keywords: Gene Rearrangement; Male; China; Lung Neoplasms; Taiwan; Administration, Oral; Kaplan-Meier Estimate; Middle Aged; Protein-Tyrosine Kinases; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Crizotinib; Japan; Carcinoma, Non-Small-Cell Lung; Proto-Oncogene Proteins; Republic of Korea; Humans; Female; Protein Kinase Inhibitors; In Situ Hybridization, Fluorescence; Aged

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.