174P - Comparison of cardiovascular effects of crizotinib and chemotherapy in patients (pts) with ALK-positive (+) advanced non-small cell lung cancer (NS...

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anticancer agents
Complications/Toxicities of Treatment
Non-Small Cell Lung Cancer
Therapy
Biological Therapy
Presenter Keith Wilner
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors K. Wilner1, T. Usari2, A. Polli2, E. Kim3
  • 1Medical Oncology, Pfizer Oncology, 92121 - La Jolla/US
  • 2Biostatistics, Pfizer Oncology, Milano/IT
  • 3Opthalmics, Pfizer Inc., New York/US

Abstract

Background

In nonclinical studies, crizotinib was identified as a mixed ion channel blocker with potential to cause QT interval prolongation. In a dog toxicity study, crizotinib treatment was associated with hemodynamic changes; increases in left ventricular end diastolic pressure, the PR interval, and the QRS complex; and decreases in myocardial contractility. We analyzed cardiac function in two ongoing phase III studies of pts with previously treated (PROFILE 1007; NCT00932893) or untreated (PROFILE 1014; NCT01154140) ALK+ advanced NSCLC.

Methods

The incidence of AEs associated with the clustered term ‘cardiac failure’ was compared between treatment arms in each study separately. Cardiac function was assessed prospectively by multigated acquisition scans or echocardiograms at baseline, cycle 3, and then every 4 cycles in all pts (PROFILE 1014) or a subgroup of pts (PROFILE 1007). The number and percentage of pts with maximum relative decreases from baseline >20% in left ventricular ejection fraction (LVEF) were calculated for pts with baseline and at least 1 post-baseline assessments.

Results

The safety populations in PROFILE 1007 and 1014 included 343 pts (crizotinib, n = 172; chemotherapy, n = 171) and 340 pts (crizotinib, n = 171; chemotherapy n = 169), respectively. In pts treated with crizotinib vs chemotherapy, AEs associated with cardiac failure occurred in 0 vs 1 (0.6%) pts in PROFILE 1007 and in 4 (2.3%) vs 1 (0.6%) pts in PROFILE 1014. After adjusting for differential treatment duration in PROFILE 1014 (median treatment duration 47 vs 18 weeks for crizotinib vs chemotherapy), the rate of cardiac failure per 1000 person-years of exposure was 22.3 vs 18.6 for pts treated with crizotinib vs chemotherapy (P = 0.87). In PROFILE 1007 and 1014, 31 and 300 pts, respectively, were evaluable for change in LVEF from baseline; in the crizotinib vs chemotherapy arms, respectively, LVEF decrease >20% occurred in 0 vs 1 (7.1%) pts in PROFILE 1007 and 4 (2.7%) vs 10 (6.7%) pts in PROFILE 1014.

Conclusions

These data suggest that crizotinib is not associated with an increased risk of cardiac failure when compared with chemotherapy in pts with ALK+ advanced NSCLC.

Clinical trial identification

NCT00932893 and NCT01154140.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

K. Wilner, T. Usari, A. Polli, E. Kim: Employee of Pfizer, Inc. and holds Pfizer stock.