Using a priority review, the FDA approved oral crizotinib (Xalkori, Pfizer) for the treatment of locally advanced or metastatic non–small-cell lung cancer (NSCLC) in patients with the anaplastic lymphoma kinase (ALK) genetic mutation, as detected by the companion test concurrently approved by the FDA. Approximately 3% to 5% of patients with NSCLC are ALK-positive.
Crizotinib “represents a paradigm shift in NSCLC treatment, where we’re moving away from a one-size-fits-all approach to biomarker-based treatment decisions,” said Paul A. Bunn, Jr, MD, the James Dudley Chair in Cancer Research, University of Colorado, Denver. Crizotinib was approved about 1 month ahead of its scheduled regulatory date.
The approval was based on 2 multicenter, single-arm trials involving 255 ALK-positive patients with locally advanced or metastatic NSCLC. In the first study, the objective response was 50%, with a median response duration of 42 weeks; in the second study, the objective response rate was 61%, with a median response of 48 weeks. Complete responses were observed in 1% of the patients.
The most common adverse reactions (≥25%) were vision disorders, nausea, diarrhea, vomiting, edema, and constipation. Grade 3 or 4 adverse reactions (in ≥4% of patients) included increased alanine transaminase levels and neutropenia. Life-threatening or fatal treatment-related pneumonitis occur red in 1.6% of pa tients within 2 months after the initiation of crizotinib therapy. The recommended dosage is 250 mg orally twice daily. (August 26, 2011)
