The FDA (Food and Drug Administration) has granted accelerated approval to Crizotinib (Xalkori) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC), advanced or metastatic ALK-positive. In conjunction with the approval of Crizotinib the FDA approved Vysis ALK Break-Apart FISH Probe Kit This diagnostic test is designed to detect rearrangements at the gene level ALK (Anaplastic Lymphoma Kinase) in NSCLC. The approval was based on two studies, Study A (n =136 patients) and Study B (n =119). Crizotinib, 250 mg was administered orally twice daily to 255 patients with lung cancer non-small cell locally advanced or metastatic ALK-positive.
The average age of patients was 52 years, 63% were Caucasian, 30% were Asian, 48% were male and 84% had an ECOG performance status of 0 or 1. Less than 3% of patients were current smokers, 96% had adenocarcinoma, 95% had metastatic disease and 94% had received prior systemic treatment for NSCLC. The primary endpoint of both trials was objective response rate (ORR) assessed by the investigator. In Study A, ORR was 50% with median response duration of 42 weeks.
In Study B, ORR was equal to 61% with median response duration of 48 weeks. Complete responses were observed in 1% of patients. No difference in the rate ORR was observed with regard to performance status, number of prior chemotherapy regimens, or percentage of cells with ALK gene rearrangement. The most common adverse reactions (at least 25%), found in both studies were vision problems, nausea, diarrhea, vomiting, edema, and constipation.
Visual disturbances included visual impairment, photopsia, vision blurred, vitreous floaters, photophobia and diplopia: grade 3-4 adverse reactions have affected at least 4% of patients and consisted of increased ALT (alanine aminotransferase) and neutropenia. In clinical studies Crizotinib has been associated with the severe form of pneumonia, treatment-related, life threatening or fatal, with a frequency of 1 .6%. The recommended dose of Crizotinib is 250 mg orally twice a day. (Xagena2011)