Atrial Fibrillation Incidence Associated With Exposure to Anticancer Drugs Used as Monotherapy in Clinical Trials

Joachim Alexandre; Louis Boismoreau; Pierre-Marie Morice; Marion Sassier; Angélique Da-Silva; Anne-Flore Plane; Jonaz Font; Paul Milliez; Damien Legallois; Charles Dolladille

doi:10.1016/j.jaccao.2022.11.019

Atrial Fibrillation Incidence Associated With Exposure to Anticancer Drugs Used as Monotherapy in Clinical Trials

JACC CardioOncol. 2023 Mar 28;5(2):216-226. doi: 10.1016/j.jaccao.2022.11.019. eCollection 2023 Apr.

Authors

Joachim Alexandre^{1

2}, Louis Boismoreau³, Pierre-Marie Morice^{1

4}, Marion Sassier², Angélique Da-Silva^{3

5}, Anne-Flore Plane⁶, Jonaz Font⁷, Paul Milliez⁸, Damien Legallois^{1

6}, Charles Dolladille^{1

2}

Affiliations

¹ Normandie University, UNICAEN, INSERM U1086 ANTICIPE, Caen, France.
² CHU de Caen-Normandie, PICARO Cardio-Oncology Program, Department of Pharmacology, Caen, France.
³ Comprehensive Cancer Center F. Baclesse, Unicancer, Caen, France.
⁴ CHU de Caen-Normandie, Department of Pharmacology, Caen, France.
⁵ PICARO Cardio-Oncology Program, Caen, France.
⁶ CHU de Caen-Normandie, PICARO Cardio-Oncology Program, Department of Cardiology, Caen, France.
⁷ CHU de Caen-Normandie, Department of Cardiology, Caen, France.
⁸ Normandie University, UNICAEN, INSERM U1237 PhIND, GIP Cyceron, Caen, France.

Abstract

Background: The incidence of atrial fibrillation (AF) associated with anticancer drugs in cancer patients remains incompletely defined.

Objectives: The primary outcome was the annualized incidence rate of AF reporting associated with exposure to 1 of 19 anticancer drugs used as monotherapy in clinical trials. The authors also report the annualized incidence rate of AF reported in the placebo arms of these trials.

Methods: The authors systematically searched ClinicalTrials.gov for phase 2 and 3 cancer trials studying 19 different anticancer drugs of interest used as monotherapy, up to September 18, 2020. The authors performed a random-effects meta-analysis to compute summary AF annualized incidence rate with its 95% CI using log transformation and inverse variance weighting.

Results: A total of 191 clinical trials (47.1% were randomized) of 16 anticancer drugs across 26,604 patients were included. Incidence rates could be calculated for 15 drugs administered singly as monotherapy. Summary annualized incidence rates of AF reporting associated with exposure to 1 of the 15 anticancer drugs used as monotherapy were derived; these ranged from 0.26 to 4.92 per 100 person-years. The 3 highest annualized incidence rates of AF reporting were found for ibrutinib 4.92 (95% CI: 2.91-8.31), clofarabine 2.38 (95% CI: 0.66-8.55), and ponatinib 2.35 (95% CI: 1.78-3.12) per 100 person-years. Summary annualized incidence rate of AF reporting in the placebo arms was 0.25 per 100 person-years (95% CI: 0.10-0.65).

Conclusions: AF reporting is not a rare event associated with anticancer drugs in clinical trials. A systematic and standardized AF detection should be considered in oncological trials, particularly those studying anticancer drugs associated with high AF rates. (Incidence of atrial fibrillation associated with anticancer drugs exposure in monotherapy, A safety meta-analysis of phase 2 and 3 clinical trials; CRD42020223710).

Keywords: anticancer drugs; atrial fibrillation; cancer; safety meta-analysis.