The U.S. Food and Drug Administration today approved crizotinib(Xalkori?, Pfizer), to treat certain patients with late-stage (locally advanced or metastatic), non-small cell lung cancers (NSCLC) who express the abnormal anaplastic lymphoma kinase (ALK) gene.

Crizotinib is being approved with a companion diagnostic test and is the second such targeted therapy approved by the FDA this year.

Genetic test
The first-of-a-kind genetic test is based on DNA Fluorescence in situ Hybridization (FISH) probe technology, a powerful means to diagnose and more efficiently treat a wide range of cancers, that will help determine if a patient has the abnormal ALK gene. The Vysis ALK Break Apart FISH Probe Kit is marketed by Abbott Laboratories.

Cancer development and growth
This ALK gene abnormality causes cancer development and growth. About 1% to 7% of those with NSCLC have the ALK gene abnormality. Patients with this form of lung cancer are typically non-smokers. Crizotinib, a pill taken twice a day as a single-agent treatment, works by blocking certain proteins called kinases, including the protein produced by the abnormal ALK gene.

?The approval of Xalkori with a specific test allows the selection of patients who are more likely to respond to the drug? said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA?s Center for Drug Evaluation and Research. ?Targeted therapies such as Xalkori are important options for treating patients with this disease and may ultimately result in fewer side effects.?

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Safety and effectiveness
Crizotinib?s safety and effectiveness were established in two multi-center, single-arm studies enrolling a total of 255 patients with late-stage ALK-positive NSCLC. A sample of a patient?s lung cancer tissue was collected and tested for the ALK gene abnormality prior to study enrollment. The studies were designed to measure objective response rate, the percentage of patients who experienced complete or partial cancer shrinkage. Most patients in the studies had received prior chemotherapy.

Study results
In one study, the objective response rate was 50% with a median response duration of 42 weeks. In another, the objective response rate was 61% with a median response duration of 48 weeks. The FDA based its approval of the Vysis ALK Break Apart FISH Probe Kit on data from one of the studies.

Crizotinib was reviewed under the FDA?s priority review program, which provides for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists.

Accelerated approval
Crizotinib and the companion Vysis ALK Break Apart FISH Probe Kit were approved ahead of the drug?s Sept. 30, 2011, FDA review goal date and the companion diagnostics? Sept. 28, 2011, review goal date.

The new drug was being approved under the FDA?s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients. The program is designed to provide patients with earlier access to promising new drugs, followed by further studies to confirm the drug?s clinical benefit.

?The trend in oncology research continues towards targeted therapies,? said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA?s Center for Devices and Radiological Health. ?This test is an example of the important role companion diagnostics play in determining that the safest and most effective treatments are promptly delivered to patients living with serious and life-threatening diseases.?

Aso read:
– ASCO 2010: Studies Report Exciting Progress Against Lung Cancer
– Investigational Lung Cancer Drug Candidate AP26113 Shows Dual Inhibition of ALK and EGFR
– Crizotinib Offers New Hope for Patients with Advanced Non-Small Cell Lung Cancer; Pfizer Submits NDA

– Crizotinib (PF-02341066) in ALK-Positive Patients with NSCLC.

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