PMID- 37713020
OWN - NLM
STAT- MEDLINE
DCOM- 20231012
LR  - 20231122
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 40
IP  - 11
DP  - 2023 Nov
TI  - Impact of Concomitant Cardiovascular Therapies on Efficacy and Safety of 
      Relugolix vs Leuprolide: Subgroup Analysis from HERO Study in Advanced Prostate 
      Cancer.
PG  - 4919-4927
LID - 10.1007/s12325-023-02634-7 [doi]
AB  - INTRODUCTION: Cardiovascular (CV) events are the leading cause of death in 
      prostate cancer. Men with prostate cancer are likely to have CV risk factors and 
      use CV-related concomitant medications. In the phase 3 HERO study, a 54% lower 
      incidence of major adverse cardiac events was reported in men treated with the 
      oral gonadotropin-releasing hormone (GnRH) receptor antagonist, relugolix, vs 
      leuprolide. Herein, we characterize the impact of concomitant CV therapies on 
      efficacy and safety in the HERO study. METHODS: In HERO, 930 men with advanced 
      prostate cancer (APC) were randomized 2:1 and treated with relugolix (120 mg 
      orally once daily; after single 360 mg loading dose) or leuprolide (injections 
      every 3 months) for 48 weeks. Subgroups analyzed included men who received 
      antihypertensives, antithrombotics, or lipid-modifying therapies (LMAs), as well 
      as the most common drug classes (> 10%) and single most common agent within each 
      class. Assessments included sustained testosterone suppression to castrate levels 
      (< 50 ng/dL) through 48 weeks and safety. RESULTS: Antihypertensives, 
      antithrombotics, and LMAs were utilized by 52.7%, 39.1%, and 39.6% of men in 
      HERO, respectively. In the main subgroups, point estimates for sustained 
      castration rates were generally consistent with overall estimates of relugolix 
      and leuprolide observed in the overall population. Sustained castration rates 
      were also mostly consistent for men taking the most common drug classes and 
      individual agents in each class (losartan [n = 103]: relugolix, 95.4% vs 
      leuprolide, 80.6%; amlodipine [n = 229]: 97.2% vs 85.5%; metoprolol [n = 88]: 
      95.7% vs 86.9%; acetylsalicylic acid [n = 259]: 97.0% vs 92.1%; clopidogrel 
      [n = 43]: 96.4% vs 86.7%; simvastatin [n = 78]: 98.0% vs 87.3%). Incidence and 
      types of adverse events (AEs) among men who received these medications were 
      mostly consistent with overall population results, with some increases in 
      grade >/= 3 and fatal AEs. CONCLUSION: Relugolix suppressed testosterone and was 
      generally well tolerated when given with concomitant CV agents. TRIAL 
      REGISTRATION: Clinical Trial ID NCT03085095. PRIOR PRESENTATION: Data presented 
      at 15th Annual Genitourinary Cancers Symposium; February 17-19, 2022, San 
      Francisco, CA, USA [Abstract 101, Poster board E11]. The published abstract from 
      this presentation can be found at 
      https://ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.101 .
CI  - (c) 2023. The Author(s).
FAU - Shore, Neal D
AU  - Shore ND
AD  - Carolina Urologic Research Center, 823 82nd Pkwy, Suite B, Myrtle Beach, SC, 
      29572, USA. NShore@gsuro.com.
FAU - Mehlhaff, Bryan A
AU  - Mehlhaff BA
AD  - Oregon Urology Institute, Springfield, OR, USA.
FAU - Cookson, Michael S
AU  - Cookson MS
AD  - Department of Urology, The University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK, USA.
FAU - Saltzstein, Daniel R
AU  - Saltzstein DR
AD  - Urology San Antonio, San Antonio, TX, USA.
FAU - Tutrone, Ronald
AU  - Tutrone R
AD  - Chesapeake Urology, Towson, MD, USA.
FAU - Brown, Bruce
AU  - Brown B
AD  - Myovant Sciences, Inc., Brisbane, CA, USA.
FAU - Lu, Sophia
AU  - Lu S
AD  - Myovant Sciences, Inc., Brisbane, CA, USA.
FAU - Fallick, Mark
AU  - Fallick M
AD  - Myovant Sciences, Inc., Brisbane, CA, USA.
FAU - Hanson, Sarah
AU  - Hanson S
AD  - Pfizer Inc., New York, NY, USA.
FAU - Saad, Fred
AU  - Saad F
AD  - University of Montreal Hospital Centre, Montreal, QC, Canada.
LA  - eng
SI  - ClinicalTrials.gov/NCT03085095
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230915
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - EFY6W0M8TG (Leuprolide)
RN  - 0 (relugolix)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 3XMK78S47O (Testosterone)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
MH  - Male
MH  - Humans
MH  - *Leuprolide/adverse effects
MH  - Antihypertensive Agents/therapeutic use
MH  - Fibrinolytic Agents/therapeutic use
MH  - Antineoplastic Agents, Hormonal/adverse effects
MH  - *Prostatic Neoplasms/drug therapy
MH  - Testosterone/therapeutic use
MH  - Gonadotropin-Releasing Hormone/therapeutic use
PMC - PMC10567896
OTO - NOTNLM
OT  - Cardiovascular agents
OT  - Leuprolide
OT  - Prostate cancer
OT  - Relugolix
COIS- Neal D. Shore-Consulting or Advisory Role: Bayer, Janssen Scientific Affairs, 
      Dendreon, Tolmar, Ferring, Medivation/Astellas, Amgen, Pfizer, AstraZeneca, 
      Genentech, Myovant Sciences. Speakers' Bureau: Janssen, Bayer, Dendreon. Bryan A. 
      Mehlhaff-Honoraria, travel, and accommodation expenses, and acted as an 
      advisor/consultant for Astellas, Amgen, Bayer, Janssen, and Pfizer; and has 
      received grants/funding from Astellas, Bayer, Janssen, and Pfizer. Michael S. 
      Cookson-Honoraria: Merck, Janssen Biotech, Bayer, Astellas Pharma, Myovant 
      Sciences. Consulting or Advisory Role: Merck, Janssen Biotech, MDxHealth, Bayer, 
      Astellas Pharma, Myovant Sciences, TesoRx Pharma, Genomic Health, Ferring 
      Pharmaceuticals, Precision Biopsy. Daniel R. Saltzstein-No relevant conflicts. 
      Ronald Tutrone-Advisory/Consulting role: Astellas, Pfizer, Myovant, Janssen, 
      Biotechne, Nymox, Dendreon. Speaker: Biotechne, Astellas, Pfizer, Myovant. Bruce 
      Brown; Sophia Lu-Employees of Myovant. Mark Fallick-Employed at Myovant at the 
      time of research and manuscript development. Sarah Hanson-Employee of Pfizer. 
      Fred Saad-Advisory roles for Astellas Pharma, AstraZeneca/MedImmune, Bayer, 
      Janssen Oncology, and Sanofi; has received honoraria from AbbVie, Amgen, Astellas 
      Pharma, AstraZeneca, Bayer, Janssen Oncology, and Sanofi; and has received 
      research funding grants provided to the institution from Astellas Pharma, 
      AstraZeneca, Bayer, Bristol Myers Squibb, Janssen Oncology, Pfizer, and Sanofi.
EDAT- 2023/09/15 12:44
MHDA- 2023/10/12 06:43
PMCR- 2023/09/15
CRDT- 2023/09/15 11:09
PHST- 2023/06/04 00:00 [received]
PHST- 2023/08/01 00:00 [accepted]
PHST- 2023/10/12 06:43 [medline]
PHST- 2023/09/15 12:44 [pubmed]
PHST- 2023/09/15 11:09 [entrez]
PHST- 2023/09/15 00:00 [pmc-release]
AID - 10.1007/s12325-023-02634-7 [pii]
AID - 2634 [pii]
AID - 10.1007/s12325-023-02634-7 [doi]
PST - ppublish
SO  - Adv Ther. 2023 Nov;40(11):4919-4927. doi: 10.1007/s12325-023-02634-7. Epub 2023 
      Sep 15.