FDA Expands Use of Crizotinib in Advanced NSCLC

New indication concerns treatment of patients with ROS-1 positive NSCLC

On 11 March, 2016 the US Food and Drug Administration (FDA) approved crizotinib (Xalkori) to treat patients with advanced (metastatic) non-small cell lung cancer (NSCLC) whose tumours have a ROS-1 gene abnormality. Crizotinib is the first and only FDA approved treatment for patients with ROS-1 positive NSCLC.

ROS-1 gene abnormalities, thought to lead to abnormal cells, have been identified in various cancers, including NSCLC. ROS-1 gene alterations are present in approximately 1% of patients with NSCLC. The overall patient and disease characteristics of NSCLC with ROS-1 gene abnormalities appear similar to NSCLC with anaplastic lymphoma kinase (ALK) gene alterations, for which crizotinib use was previously approved. Crizotinib was approved to treat certain patients with late-stage NSCLC that expresses an abnormal ALK gene in 2011.

Dr Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said: “The expanded use of Xalkori will provide a valuable treatment option for patients with the rare and difficult to treat ROS-1 gene mutation by giving health care practitioners a more personalized way of targeting ROS-1 positive NSCLC.”

Crizotinib is an oral medication that blocks the activity of the ROS-1 protein in tumours that have ROS-1 gene alterations. This effect on ROS-1 may prevent NSCLC from growing and spreading.

The safety and efficacy of crizotiib for the treatment of patients with ROS-1 positive tumours were evaluated in a multi-center, single-arm study of 50 patients with ROS-1 positive metastatic NSCLC. Patients received crizotinib twice daily to measure the overall response rate. Results showed 66% of participants experienced a complete or partial shrinkage of their NSCLC tumours, an effect that lasted a median of 18.3 months.

The safety results of this study were generally consistent with the safety profile of crizotinib evaluated in 1,669 patients with ALK-positive metastatic NSCLC.

The most common side effects of crizotinib are vision disorders, nausea, diarrhoea, vomiting, oedema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, and dizziness and neuropathy. Crizotinib may cause serious side effects, including liver problems, life-threatening or fatal inflammation of the lungs, arrhythmia and partial or complete loss of vision in one or both eyes.

The FDA granted the crizotinib expanded use application breakthrough therapy designation and priority review status. These are distinct programmes intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions. Crizotinib also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs for rare diseases.

The recommended dose for crizotinib is 250 mg taken orally twice daily.

Xalkori is marketed by Pfizer, based in New York, New York.