Crizotinib produces a clinically meaningful and durable benefit among East Asian patients with c-ros oncogene 1 (ROS1)-positive advanced non-small cell lung cancer (NSCLC), according to a study published in the Journal of Clinical Oncology.1
ROS1 mutations are found in approximately 1% to 2% of patients with NSCLC, with an uptick to 2% to 3% among patients of East Asian descent. Previous studies have demonstrated that crizotinib — a tyrosine kinase inhibitor (TKI) of ALK, MET, and ROS1 kinases — has markedly increased antitumor activity in this population.
For this open-label phase 2 study (ClinicalTrials.gov Identifier: NCT01945021), researchers treated 127 patients with ROS1-positive advanced NSCLC with oral crizotinib 250 mg twice daily. Eligible patients had received 3 or less prior systemic treatments.
All 127 patients were evaluable for safety and efficacy analysis, and by time of data cut-off approximately 50% of patients were still receiving treatment.
The overall response rate was 71.7% (95% CI, 63.0%-79.3%), with 74 and 17 patients achieving partial and complete responses, respectively, and was similar among patients regardless of the number of prior systemic therapies they had received. Treatment responses were found to be durable, lasting 19.7 months (95% CI, 14.1-not reached).
The median progression-free survival (PFS) was 15.9 months (95% CI, 12.9-24.0); patients with brain metastases had a PFS of 10.2 months compared with 18.8 months among patients without brain metastases, but the authors noted that the small sample size was a limitation for this particular analysis.
Results showed that median overall survival was 32.5 months (95% CI, 32.5 months-not evaluable), but data was considered to be immature at the time of analysis.
The safety profile remained consistent with those previously reported. The most frequently reported adverse events included elevated transaminases, vision disorders, nausea, vomiting, and diarrhea.
The authors concluded that “results from this study, to our knowledge the largest phase II trial in ROS1-positive advanced NSCLC to date, provides additional compelling clinical evidence to support the use of crizotinib in this molecular subgroup of patients with NSCLC.”
- Wu YL, Yang JCH, Kim DW, et al. Phase II study of crizotinib in East Asian patients with ROS1-positive advanced non-small-cell lung cancer [published online March 2, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.75.5587