On March 11, 2016, the U. S. Food and Drug Administration approved crizotinib capsules (Xalkori, Pfizer, Inc.) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive. Crizotinib was first approved in 2011 for the treatment of patients whose tumors are anaplastic lymphoma kinase (ALK)-positive.
The current approval was based on a multicenter, single-arm trial in patients with metastatic ROS1 rearrangement-positive NSCLC. All patients received crizotinib 250 mg orally twice daily. The efficacy outcome measures were objective response rate (ORR) according to RECIST v1.0 as evaluated by an independent radiology review (IRR) and as evaluated by the investigators. Duration of response (DoR) was an additional outcome measure.
The trial enrolled 50 patients with an age range of 25-77 years whose tumors were prospectively determined to be ROS1-positive by fluorescence in situ hybridization (FISH; 96%) or reverse transcription polymerase chain reaction (RT-PCR; 4%) clinical trial assays. The ORR by IRR was 66% (95% CI: 51%, 79%) with a median DoR of 18 months. The ORR according to investigators was 72% (95% CI: 58%, 84%).
The safety results of this trial were generally consistent with the safety profile of crizotinib evaluated in 1,669 patients with ALK-positive metastatic NSCLC. The most common adverse reactions of Xalkori are vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy.
The recommended dose and schedule for crizotinib is 250 mg capsules taken by mouth twice daily.
This application was approved before the Prescription Drug User Fee Act (PDUFA) goal date of April 8, 2016. Crizotinib received Breakthrough Therapy Designation for the ROS1-positive development program and the application was granted Priority Review. A description of these expedited programs is in the Guidance for Industry:
Expedited Programs for Serious Conditions-Drugs and Biologics, available at:http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202570s016lbl.pdf