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

Abstract

On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved crizotinib (XALKORI 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% confidence intervals (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 on the basis of the high ORRs 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. Clin Cancer Res; 20(8); 2029-34. Ó2014 AACR.

Molecular characterization of pulmonary sarcomatoid carcinoma: analysis of 33 cases

“…Crizotinib is a multitargeted tyrosine kinase inhibitor with activity against MET, ALK, and ROS1, that is an effective treatment for many patients with ALK-rearranged lung cancer. 15,[49][50][51][52] However, virtually all patients develop resistance to crizotinib therapy, usually within 1 year. [53][54][55][56][57][58][59] The higher potency ALK tyrosine kinase inhibitor ceritinib has been studied in both crizotinib-naive and crizotinib-resistant patients and has received Food and Drug Administration approval for crizotinib-resistant or -intolerant ALKrearranged lung carcinoma.…”

“…[11][12][13][14] Currently, tumors with ALK rearrangement and EGFR mutations have molecular targeted therapies approved by the US Food and Drug Administration. Crizotinib and ceritinib are approved for use in ALK rearranged tumors, [15][16][17] while erlotinib, gefitinib, and afatinib are approved for tumors with EGFR mutations. [18][19][20][21] In the US population, these therapies are applicable to a minority of patients with lung carcinoma, as ALK rearrangement is present in o 5% of lung adenocarcinomas and EGFR mutations are present in 15-25% of lung adenocarcinomas.…”

Real-World Outcomes in Patients with Alk-Positive Non-Small Cell Lung Cancer Treated with Crizotinib

“…Several epidermal growth factor receptor (egfr) and anaplastic lymphoma kinase (alk) inhibitors are now approved that have shown substantial response rates in patients with nsclc who have certain egfr mutations and alk rearrangements [7][8][9][10] . Crizotinib, for example, has been shown in clinical studies to be associated with tumour reduction or stabilization in 90% of alk+ patients, with response duration of up to 15 months 11 and superior efficacy versus standard chemotherapy 12,13 .…”

FDA Approval: Ceritinib for the Treatment of Metastatic Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer

“…Potentially targetable oncogenes in NSCLC have been identified in over half of lung adenocarcinomas and about 30% of squamous cell lung carcinomas (1,2). The discovery of the ALK gene rearrangement in 2007 as an oncogenic "driver" mutation in about 5% of patients with NSCLC paved the way for the development of the ALK tyrosine kinase inhibitor (TKI) crizotinib, which received FDA accelerated approval in 2011 and traditional (i.e., regular) approval in 2013 (3)(4)(5).…”