Crizotinib in East Asian Patients With ROS1-Positive Advanced NSCLC


Key Points

  • Objective response was observed in 72% of patients.
  • Median duration of response was 19.7 months.

In a phase II study reported in the Journal of Clinical Oncology, Wu et al found that crizotinib (Xalkori) was highly active in East Asian patients with ROS1-positive advanced non­–small cell lung cancer (NSCLC).

Study Details

In the study, 127 patients from 37 sites in China, Japan, South Korea, and Taiwan who had received three or fewer lines of prior systemic therapy were enrolled between September 2013 and January 2015 and treated with crizotinib at 250 mg twice daily until disease progression or unacceptable toxicity. Progression was determined using RECISTv1.1 criteria on independent radiology review. At investigator discretion, patients could continue treatment beyond RECIST-defined progression if ongoing clinical benefit was observed. Metastatic disease was present in 95% of patients, 72% had no history of smoking, 19% had no prior therapy for advanced disease, and 39% had 2 or 3 prior lines of therapy.

The primary endpoint was objective response rate on independent radiology review.


At data cutoff in July 2016, 49.6% of patients were still receiving treatment. Objective response was observed in 92 patients (71.7%), including complete response in 17 (13%). Clinical benefit was observed irrespective of presence of brain metastases at baseline, number of prior lines of chemotherapy, enrollment country, age, sex, smoking status, or performance status. Response rates were similar irrespective of the number of prior lines of therapy. Median duration of response was 19.7 months. Median progression-free survival was 15.9 months. Median overall survival was 32.5 months, with 1-year survival of 83.1%. Of 63 patients with progression while on crizotinib, 43 (68.3%) continued treatment with crizotinib for ≥ 3 weeks post-progression.

Adverse Events

The most common treatment-related adverse events of any grade were elevated transaminases (55.1%), vision disorder (48.0%), nausea (40.9%), diarrhea (38.6%), and vomiting (32.3%). Treatment-related grade ≥ 3 adverse events occurred in 25.2% of patients, with the most common being neutropenia (10.2%) and elevated transaminases (5.5%). A treatment-related adverse event (diarrhea) led to discontinuation of treatment in 1 patient (0.8%).

The investigators concluded, “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.”

The study was supported by OxOnc Development and Pfizer.

Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangzhou, is the corresponding author for the Journal of Clinical Oncology article. 

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