FDA Expands Label for Crizotinib (Xalkori) to Include ROS1-Positive Lung Cancer

Treatment achieves 66% response rate

The FDA has approved a supplemental new drug application for crizotinib (Xalkori, Pfizer) to treat patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors are ROS1-positive. In 2015, the FDA granted breakthrough therapy and priority review designations for this indication. Crizotinib also is indicated for patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test.

ROS1 rearrangements occur when the ROS1 gene attaches to another gene and changes the way each gene normally functions, which can contribute to cancer cell growth. Epidemiology data suggest that ROS1 rearrangements occur in approximately 1% of NSCLC patients. Of the estimated 1.5 million new cases of NSCLC worldwide each year, approximately 15,000 may be driven by oncogenic ROS1 fusions.

The FDA’s approval was based on results from a single-arm phase 1 trial in which 50 patients with ROS1-positive metastatic NSCLC were treated with oral crizotinib (250 mg twice daily). The study’s efficacy outcome measures were the objective response rate and the duration of response.

Crizotinib showed marked antitumor activity in patients with ROS1-positive metastatic NSCLC, with an objective response rate of 66%, as determined by an independent radiology review. There was one complete response and 32 partial responses. The median duration of response was 18.3 months.

An FDA-approved test for the detection of ROS1 rearrangements in NSCLC is not currently available. A companion diagnostic test is under development to identify patients with ROS1-positive metastatic NSCLC who may benefit from treatment with crizotinib.

Crizotinib was the first ALK inhibitor approved in the U.S. and has been used to treat more than 8,000 patients.

Source: Pfizer; March 11, 2016.