Abstract 1595P
Background
The cyclin-dependent kinases (CDK)4/6 inhibitors abemaciclib, palbociclib and ribociclib are approved for the treatment of hormone receptor-positive metastatic breast cancer. These drugs are equally effective according to literature, however, ribociclib is associated with concentration-dependent QTc-prolongation. This complicates ribociclibs use in patients, as pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) resulting in QTc-prolongation might occur with concomitant medications. The aim of this abstract is to check for possible QTc-prolongation DDIs using the Drug Interaction Checker developed by Radboudumc and University of Liverpool (https://cancer-druginteractions.org/).
Methods
All DDIs searched in combination with each CDK4/6 inhibitor on the website between January 1 and December 31, 2021 were evaluated. The requested information included the number of hits per DDI and interaction colour (red = contra-indication, amber = potential interaction, yellow = potential weak interaction, or green = no interaction). Red and amber DDIs were considered clinically relevant. All DDIs possibly related to QTc-prolongation were identified.
Results
Of 13,963 DDIs searched with CDK4/6 inhibitors, 4,360 were related to abemaciclib, 6,062 to palbociclib and 3,541 to ribociclib (all related to n=409 drugs). In total, 987 (6.8%) DDIs were related to QTc-prolongation. Ribociclib and abemaciclib had respectively 592 (16.7%) and 196 (4.5%) red and 1,078 (30.4%) and 177 (2.9%) amber DDIs. Of those, respectively 443 (12.5%) and 33 (0.7%) red and 75 (2.1%) and 60 (1.4%) amber DDIs were related to QTc-prolongation. Palbociclib had 158 (3.6%) and 264 (4.4%) amber DDIs. None were related to QTc-prolongation. The most frequently searched DDIs with ribociclib were with amitriptyline, citalopram and escitalopram (60, 23 and 22 hits, respectively).
Conclusions
There were more clinically relevant DDI hits related to ribociclib compared to abemaciclib and palbociclib. A large number of red-flagged ribociclib DDIs were related to QTc-prolongation, which seems to be a known unfavourable effect of ribociclib. Therefore, practical guidelines on how to cope with QTc-prolongation DDIs with ribociclib are required.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Chiong: Financial Interests, Institutional, Funding, To Liverpool University: BMS, Gilead, Ipsen, Pfizer; Financial Interests, Institutional, Full or part-time Employment, To Liverpool University: Janssen. J. Martin: Financial Interests, Institutional, Funding, To Liverpool University: BMS, Gilead, Ipsen, Janssen, Pfizer. N.V. Erp: Financial Interests, Institutional, Research Grant, To Radboudumc, not related to this work: KWF, ZonMW, Astellas, Ipsen, Janssen Cilag; Financial Interests, Institutional, To Radboudumc (honoraria for lectures), not related to this work: Sanofi, Bayer, Pfizer. All other authors have declared no conflicts of interest.