Efficacy and safety of crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Poster Discussion Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 8032)
Sai-Hong Ignatius Ou, Yung-Jue Bang, D. Ross Camidge, Gregory J. Riely, Ravi Salgia, Geoffrey Shapiro, Benjamin J. Solomon, Jeffrey A. Engelman, Eunice Lee Kwak, Jeffrey W. Clark, Lesley Tye, Keith D. Wilner, Patricia Stephenson, Marileila Varella-Garcia, Kristin Bergethon, Anthony John Iafrate, Alice Tsang Shaw; Chao Family Comprehensive Cancer Center, Orange, CA; Seoul National University Hospital, Seoul, South Korea; University of Colorado Cancer Center, Aurora, CO; Memorial Sloan-Kettering Cancer Center, New York, NY; The University of Chicago, Chicago, IL; Dana-Farber Cancer Institute, Boston, MA; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Massachusetts General Hospital Cancer Center, Boston, MA; Division of Hematology and Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Pfizer Oncology, La Jolla, CA; Rho, Inc., Chapel Hill, NC; University of Colorado School of Medicine, Aurora, CO; Duke University School of Medicine, Durham, NC; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: ROS1 receptor tyrosine kinase rearrangements define a subset of NSCLC sensitive to the small-molecule tyrosine kinase inhibitor crizotinib, approved multinationally for the treatment of advanced ALK-positive NSCLC. Updated efficacy and safety data are presented for crizotinib in patients with advanced ROS1-rearranged NSCLC. Methods: ROS1 status was determined by break-apart FISH assays, and patients were enrolled into an expansion cohort of an ongoing phase 1 crizotinib study (NCT00585195). Patients received crizotinib 250 mg BID. Responses were assessed using RECIST v1.0. The disease control rate (DCR; % stable disease [SD] + partial response [PR] + complete response [CR]) was evaluated at weeks 8 and 16. Results: At the data cut-off, 33 patients with ROS1-positive NSCLC had enrolled, and 31 had received crizotinib, with 25 evaluable for response. Median age was 51 years (range 31–72), 79% of patients were never-smokers and 97% had adenocarcinoma histology. The median number of prior treatments for advanced disease was 1 (range 0–7). The objective response rate (ORR) was 56% (95% CI: 24.4–65.1), with 2 CRs, 12 PRs and 8 SDs. 8-week and 16-week DCRs were 76% and 60%, respectively. Median PFS has not been reached, with ~60% of patients still in follow-up for PFS; 6-month PFS probability was 71% (95% CI: 45.6–86.0). Median treatment duration was 24 weeks (range 2.3–112), and 24 patients were on treatment at the data cut-off; 5 patients died (all disease-related). 91% of patients had treatment-related adverse events (AEs): most commonly visual impairment (82%), nausea (36%) and diarrhea (33%). Most AEs were grade 1 in severity. Peripheral edema and elevated transaminases were also reported, similar to the previous experience of crizotinib. There were no treatment-related serious AEs or treatment-related permanent discontinuations. Accrual of patients with ROS1-positive NSCLC is ongoing. Conclusions: As observed in ALK-positive NSCLC, crizotinib had dramatic antitumor activity with a high ORR (56%) in patients with ROS1-positive NSCLC and a generally tolerable and manageable AE profile. These findings indicate that crizotinib is an effective therapy for advanced ROS1-positive NSCLC. Clinical trial information: NCT00585195.