Crizotinib has been approved to treat locally advanced and metastatic non–small cell lung cancers that express an abnormal anaplastic lymphoma kinase gene, the Food and Drug Administration announced on Aug. 26.
Crizotinib (Xalkori, Pfizer) was approved for the indication in concert with a companion diagnostic test for ALK gene abnormality, called the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.). Up to 7% of those with NSCLC – typically patients without a history of smoking – have the ALK gene abnormality. Crizotinib, a kinase inhibitor, is a single-agent oral therapy.
"The approval of Xalkori with a specific test allows the selection of patients who are more likely to respond to the drug," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in a press release announcing the approval. "Targeted therapies such as Xalkori are important options for treating patients with this disease and may ultimately result in fewer side effects."
Crizotinib’s safety and effectiveness were established in two multicenter, single-arm studies enrolling a total of 255 patients with late-stage ALK-positive NSCLC. The studies were designed to measure the percentage of patients who experienced complete or partial cancer shrinkage. Most patients in the studies had received prior chemotherapy.
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.
Crizotinib was approved under the FDA’s accelerated approval program, which allows approvals based on clinical data showing a drug’s effect on an end point that is reasonably likely to predict clinical benefit. Further studies will confirm the drug’s clinical benefit.
The most common side effects reported in patients receiving crizotinib included vision disorders, nausea, diarrhea, vomiting, edema, and constipation. Crizotinib has also been associated with potentially life-threatening pneumonitis, which necessitates discontinuation of the drug. Pregnancy also is a contraindication for crizotinib use.