PMID- 35141028 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220211 IS - 2156-6976 (Print) IS - 2156-6976 (Electronic) IS - 2156-6976 (Linking) VI - 12 IP - 1 DP - 2022 TI - Concomitant use of oral anticoagulants in patients with advanced prostate cancer receiving apalutamide: A post-hoc analysis of TITAN and SPARTAN studies. PG - 445-450 AB - Apalutamide, an androgen receptor signaling inhibitor, in combination with androgen-deprivation therapy (ADT), is approved for treatment of patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer, based on the data from the phase 3 SPARTAN and TITAN studies respectively. Apalutamide is an inducer of cytochrome P450 enzymes and P-glycoprotein, which are involved in the metabolism of oral anticoagulants (OACs) and may thus have potential drug-drug interactions when co-administered with OACs. Concomitant use of certain OACs such as apixaban, rivaroxaban, edoxaban, dabigatran, and warfarin was allowed in the SPARTAN and TITAN studies. A post-hoc analysis was conducted to evaluate the incidence of treatment-emergent thrombotic and embolic adverse events (AEs) in patients receiving concomitant OACs with apalutamide + ADT or placebo + ADT in both the studies. Anticoagulants were identified by WHO Drug Anatomical Therapeutic Chemical level 4 classifications. Thrombotic and embolic AEs were coded using the Medical Dictionary for Regulatory Activities Version 22.1. Data were analyzed from patients receiving concurrent OACs among all treated patients in SPARTAN (apalutamide + ADT: 95/803 [11.8%]; placebo + ADT: 48/398 [12.1%]) and TITAN (apalutamide + ADT: 31/524 [5.9%]; placebo + ADT: 28/527 [5.3%]). No consequential differences were observed in the occurrence of thrombotic and embolic events between apalutamide + ADT and placebo + ADT groups receiving concomitant OACs in SPARTAN (11.6% vs 12.5%) or TITAN (19.4% vs 21.4%). Grade 3/4 thrombotic and embolic AEs observed in patients receiving concomitant OACs with apalutamide + ADT or placebo + ADT were 6 (6.3%) vs 5 (10.4%) in SPARTAN and 3 (9.7%) vs 1 (3.6%) in TITAN. This analysis suggests that when necessary, concomitant OACs can be used with apalutamide with appropriate monitoring. CI - AJCR Copyright (c) 2022. FAU - Potdar, Rushikesh AU - Potdar R AD - Medical Group Oncology, Janssen Pharmaceuticals Horsham, PA, USA. FAU - Gartrell, Benjamin A AU - Gartrell BA AD - Departments of Medical Oncology and Urology, Montefiore Einstein Center for Cancer Care Bronx, NY, USA. FAU - Given, Robert AU - Given R AD - Urology of Virginia, Eastern Virginia Medical School Norfolk, VA, USA. FAU - Karsh, Lawrence AU - Karsh L AD - The Urology Center of Colorado Denver, CO, USA. FAU - Frankel, Jeffrey AU - Frankel J AD - Seattle Urology Research Center Seattle, WA, USA. FAU - Nenno, Karen AU - Nenno K AD - SCL Health-Lutheran Medical Center Wheat Ridge, CO, USA. FAU - O'MalleyLeFebvre, Kris AU - O'MalleyLeFebvre K AD - SCL Health-Lutheran Medical Center Wheat Ridge, CO, USA. FAU - Bhaumik, Amitabha AU - Bhaumik A AD - Janssen Research and Development Raritan, NJ, USA. FAU - McCarthy, Sharon AU - McCarthy S AD - Janssen Research and Development Raritan, NJ, USA. FAU - McGowan, Tracy AU - McGowan T AD - Medical Group Oncology, Janssen Pharmaceuticals Horsham, PA, USA. FAU - Pieczonka, Christopher AU - Pieczonka C AD - Associated Medical Professionals of New York Syracuse, NY, USA. LA - eng PT - Journal Article DEP - 20220115 PL - United States TA - Am J Cancer Res JT - American journal of cancer research JID - 101549944 PMC - PMC8822273 OTO - NOTNLM OT - Apalutamide OT - anti-coagulants OT - comedication OT - drug-drug interaction OT - thromboembolic adverse events COIS- Benjamin A Gartrell: Personal fees from Exelixis Inc, Pfizer, Janssen, Genomic Health, and EMD Serono, outside the submitted work. Robert Given: Speaker for Janssen, Myovant and Bayer; Investigator for research trials with Janssen, Bayer, Tavanta, Merck, and Pfizer. Lawrence Karsh: Honoraria from Astellas, Bayer, Janssen, Pfizer and Dendreon; Consultancy for 3D Biopsy, Astellas, Astra-Zeneca, Bayer, Dendreon, Ferring, Janssen, Pfizer, and Vaxiion; Speakers' Bureau: Astellas, Bayer, Janssen, Pfizer, and Clovis; received Travel, Accommodations, Expenses from Astellas, Bayer, Janssen, Pfizer, and Dendreon; received research funding from Astellas, Astra Zeneca, Bayer, BioXcel Therapeutics, Bristol Meyers Squibb, CU Optics, CUSP, Dendreon, Epizyme, Exact Sciences, Ferring, FKD, Genentech/Roche, GenomeDx, Genomic Health, Janssen, Merck, Myovant, Nucleix, OncoCell MDx, Pfizer, Pharmtech/Veru, Precision Med, QED Therapeutics, Siemens, Urogen, and Vaxiion; Stock Owner: Swan Valley Medical. Jeffrey Frankel: Investigator for Urovant Sciences; Investigator and speaker for Astellas Pharma and Pfizer Inc.; Speaker for Tolmar Inc. Karen Nenno: Consulting fees from Karyopharm to participate in an advisory board. Kris O'MalleyLeFebvre: Nothing to disclose. Christopher Pieczonka: Consultancy: Dendreon, Bayer, Astra Zeneca, Merck, LUGPA, UroGPO, Janssen, Astellas, Pfizer, Foundation Medicine, Sun; Compensated Research Studies: Dendreon, Bayer, Astra Zeneca, Merck, Janssen, Astellas, Pfizer, Very, Eli-Lilly, Laekna. Rushikesh Potdar and Tracy McGowan: Employees of Janssen Pharmaceuticals and own stock in Johnson and Johnson, of which Janssen is a wholly owned subsidiary. Amitabha Bhaumik and Sharon McCarthy: Employees of Janssen Research & Development, LLC and own stock in Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary. EDAT- 2022/02/11 06:00 MHDA- 2022/02/11 06:01 PMCR- 2022/01/15 CRDT- 2022/02/10 05:37 PHST- 2021/10/11 00:00 [received] PHST- 2021/12/20 00:00 [accepted] PHST- 2022/02/10 05:37 [entrez] PHST- 2022/02/11 06:00 [pubmed] PHST- 2022/02/11 06:01 [medline] PHST- 2022/01/15 00:00 [pmc-release] PST - epublish SO - Am J Cancer Res. 2022 Jan 15;12(1):445-450. eCollection 2022.