FDA Approves Crizotinib for ROS1 Rearranged Advanced NSCLC

March 11, 2016

The FDA has announced its approval of crizotinib (Xalkori) for the treatment of patients with non–small-cell lung and ROS1 rearrangements.

The US Food and Drug Administration (FDA) has announced its approval of crizotinib (Xalkori) for the treatment of patients with non–small-cell lung cancer (NSCLC) and ROS1 rearrangements. The targeted treatment crizotinib was initially approved in 2011 for patients with NSCLC and ALK mutations. 

Research has shown that ROS1 rearrangements are estimated to occur in about 1% of patients with NSCLC and are seen more commonly in patients who are never smokers or light smokers, and who have features of adenocarcinoma.

“Lung cancer is difficult to treat, in part, because patients have different mutations, some of which are rare,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “The expanded use of [crizotinib] will provide a valuable treatment option for patients with the rare and difficult to treat ROS1 gene mutation by giving health care practitioners a more personalized way of targeting ROS1-positive NSCLC.”

The FDA based its approval on efficacy data taken from a single-arm study of crizotinib in 50 patients with NSCLC and ROS1 rearrangements. The study, published in the New England Journal of Medicine in 2014, assigned patients with advanced disease to an oral dose of 250 mg crizotinib twice daily. The median age of patients in the study was 50.

Investigator assessed objective response rate was 72% (95% CI, 58–84). The objective response rate according to RECIST v1.0 as evaluated by independent radiology review was 66% (95% CI, 51–79). Three patients had a complete response to therapy and 33 had partial responses. The median duration of response was 17.6 months with a median progression-free survival of 19.2 months.

According to the FDA, the safety of crizotinib in patients with ROS1 rearrangements was consistent with that seen in larger trials of patients with ALK-positive metastatic NSCLC. The most common adverse effects seen in patients were vision disorders (82%), nausea (40%), diarrhea (44%), vomiting (34%), edema (40%), and constipation (34%). The most common grade 3 adverse events reported in the phase I trial were neutropenia (10%), hypophosphatemia (10%), and an elevated level of alanine aminotransferase (4%).