FDA approves Xalkori (crizotinib) to treat NSCLC patients whose tumours are ROS1-positive- Pfizer

Pfizer announced that the FDA has approved a supplemental New Drug Application (sNDA) for Xalkori (crizotinib) to treat patients with metastatic non-small cell lung cancer (NSCLC) whose tumours are ROS1-positive. In 2015, the FDA granted Breakthrough Therapy and Priority Review designations for this indication. Crizotinib is also indicated for patients with metastatic NSCLC whose tumours 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 cases. Of the estimated 1.5 million new cases of NSCLC worldwide each year, roughly 15,000 may be driven by oncogenic ROS1 fusions.

The approval is based on a multicentre, single-arm Phase I study (Study 1001) that included 50 patients with ROS1-positive metastatic NSCLC treated with 250 mg of crizotinib orally twice daily. The efficacy outcome measures in this study were objective response rate and duration of response. The results of this study showed that crizotinib exhibited marked anti-tumour activity in patients with ROS1-positive metastatic NSCLC, with an objective response rate of 66% (95% CI: 51–79%) by an independent radiology review. There was one complete response and 32 partial responses. The median duration of response was 18.3 months (95% CI: 12.7 months–not reached). Additionally, the safety profile of crizotinib in ROS1-positive metastatic NSCLC was generally consistent with that observed in patients with ALK-positive metastatic NSCLC. An FDA-approved test for the detection of ROS1 rearrangements in NSCLC is not currently available; however, laboratory developed tests are available. A companion diagnostic test is currently under development to identify patients with ROS1-positive metastatic NSCLC who may benefit from treatment with crizotinib.

Comment: The European Medicines Agency (EMA) is reviewing an application to extend the marketing authorization of crizotinib to include the treatment of adult patients with ROS1-positive advanced NSCLC. In Europe, Xalkori is indicated for the first-line treatment of adults with ALK-positive advanced NSCLC and for the treatment of adults with previously treated ALK-positive advanced NSCLC.