Comparison of cardiovascular effects of crizotinib and chemotherapy in ALK-positive advanced non-small-cell lung cancer

Future Oncol. 2019 Apr;15(10):1097-1103. doi: 10.2217/fon-2018-0869. Epub 2019 Jan 17.

Abstract

Aim: We analyzed cardiac function in two Phase III studies of previously treated (PROFILE 1007) or untreated (PROFILE 1014) ALK-positive advanced non-small-cell lung cancer.

Patients & methods: Adverse events associated with cardiac failure were compared between treatment arms in each study separately. Cardiac function was assessed prospectively by multigated acquisition scans or echocardiograms.

Results: In PROFILE 1007 and 1014, incidence of cardiac failure adverse events was 0% (crizotinib) versus 0.6% (chemotherapy) and 2.3% versus 0.6%, respectively. In crizotinib versus chemotherapy arms, respectively, >20% left ventricular ejection fraction decreases occurred in 0/19 (0%) versus 1/16 (6.3%) patients from PROFILE 1007 and 4/150 (2.7%) versus 10/150 (6.7%) patients from PROFILE 1014.

Conclusion: These analyses did not reveal any clinically meaningful changes in myocardial function with crizotinib in patients with ALK-positive non-small-cell lung cancer. Clinicaltrials.gov identifier: PROFILE 1007, NCT00932893; PROFILE 1014, NCT01154140.

Keywords: ALK; LVEF; cardiac function; crizotinib; non-small-cell lung cancer; safety.

Publication types

  • Comparative Study

MeSH terms

  • Anaplastic Lymphoma Kinase / metabolism*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cardiotoxicity
  • Clinical Trials, Phase III as Topic
  • Crizotinib / adverse effects*
  • Follow-Up Studies
  • Heart Failure / chemically induced*
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Prognosis
  • Prospective Studies
  • Protein Kinase Inhibitors / adverse effects*
  • Randomized Controlled Trials as Topic

Substances

  • Protein Kinase Inhibitors
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase

Associated data

  • ClinicalTrials.gov/NCT00932893
  • ClinicalTrials.gov/NCT01154140