The FDA has agreed to fast-track its review of Pfizer's New Drug Application for crizotinib, an investigational small molecular inhibitor for patients with advanced lung cancer who test positive for the anaplastic lymphoma kinase (ALK) translocation. According to the National Cancer Institute, approximately 2% to 7% of patients with non-small cell lung cancer (NSCLC) have a chromosomal rearrangement involving the ALK gene (most often, an EML4-ALK translocation). This accounts for approximately 10,000 cases annually in the United States.
Data from a small phase I trial, conducted by Kwak and associates, were published in the New England Journal of Medicine last year and reported a 57% response rate in previously treated patients with ALK-positive NSCLC. The rate of disease control at 8 weeks was 87%. Historically, only about 10% of patients with NSCLC respond to second-line therapeutics, so although this trial was a single-arm study lacking a control arm, it was attention-getting.
Of note, all the patients in the study by Kwak and colleagues were ALK-positive and most were nonsmokers. The majority of adverse events reported by the authors were grade 2 or less. The most common were mild nausea, vomiting, diarrhea, and mild visual disturbances. Some patients had elevated liver function tests.
A study presented at the American Society of Clinical Oncology in 2010 by Shaw and associates reported that ALK-positive patients respond poorly to standard chemotherapy and epithelial growth factor inhibitors. Bang and colleagues, who presented data from a phase II study of crizotinib at the meeting's plenary session, expressed optimism that crizotinib would improve survival over conventional therapy for these patients.
However, another study published late last year found that some ALK-positive patients treated with crizotinib have or develop other mutations along the ALK pathway that confer resistance to the drug. Researchers are already investigating agents that might bind to these mutated ALK proteins and have less likelihood of being resisted.
In a press release, Pfizer said it expects to complete its submission to the FDA by June 2011. If crizotinib is approved, the company says it could have it on the market in the first quarter of 2012.