Efficacy of crizotinib inhibiting specific molecular pathways in non-small-cell lung carcinoma

Abstract

The US FDA granted approval for crizotinib as the first-line treatment for patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearranged metastatic non-small-cell lung cancer, on November 20, 2013. Crizotinib is a customized and improved therapeutic option for patients with non-small-cell lung cancer that enhances overall survival without increasing toxicity. In the future, new targeted therapies may achieve additional indications for treating patients with lung cancer. This article summarizes data from crizotinib studies.

Keywords:

• anaplastic lymphoma kinase
• crizotinib
• c-ros1
• echinoderm microtubule-associated protein-like 4
• met/hepatocyte growth factor receptor
• non-small-cell lung cancer

Financial & competing interests disclosure

HR Mirshahidi has served as a consultant to BoehringerIngelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Crizotinib is very effective in treatment of non-small-cell lung cancer (NSCLC) patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (ALK) translocation. This first-line ALK inhibitor achieved responses in 60% of patients, with progression-free survival ranging between 8 and 11 months.

• The US FDA and EMA, Committee for Medicinal Products for Human Use, granted approval for crizotinib for the treatment of ALK rearrangement-positive NSCLC, based on data from the PROFILE 1007 study.

• Comprehensive Cancer Network guidelines recommend crizotinib as first-line therapy in patients with locally advanced or metastatic NSCLC who carry ALK-positive tumor.

• Crizotinib is also effective in ROS1-rearranged and c-Met-amplified NSCLC.

• The toxicities of crizotinib are manageable; however, hepatotoxicity and pneumonitis are serious complications.

• Crizotinib could also be effective in patients with other malignancies.

• Lowering the cost of the screening test and reducing the drug price at the same time will improve cost–effectiveness of crizotinib.