Scientific Publications by FDA Staff

Clin Cancer Res 2014 Apr 15;20(8):2029-34

U.S. Food and Drug Administration Approval: Crizotinib for Treatment of Advanced or Metastatic Non-small Cell Lung Cancer that Is Anaplastic Lymphoma Kinase Positive.

Malik SM, Maher VE, Bijwaard KE, Becker RL, Zhang L, Tang SW, Song P, Liu Q, Marathe A, Gehrke B, Helms W, Hanner D, Justice R, Pazdur R

On August 26, 2011, the U.S. Food and Drug Administration approved crizotinib (XALKORI(R) Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was 61% (95% CI: 52%, 70%) with a median response duration of 48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the ORR was 50% (95% CI: 42%, 59%) with a median response duration of 42 weeks. The most common adverse reactions (>/=25%) were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Accelerated approval was granted based on the high objective response rates and durable responses. On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen.