TY - JOUR
T1 - An Expert Review on the Combination of Relugolix With Definitive Radiation Therapy for Prostate Cancer
AU - Roy, Soumyajit
AU - Zaorsky, Nicholas G.
AU - Bagshaw, Hilary P.
AU - Berlin, Alejandro
AU - Tree, Alison
AU - Turner, Sandra
AU - Koontz, Bridget
AU - Nguyen, Paul
AU - Chen, Ronald
AU - Dess, Robert T.
AU - Jackson, William C.
AU - Kishan, Amar U.
AU - Stish, Bradley
AU - Nagar, Himanshu
AU - Posadas, Edwin
AU - Tran, Phuoc T.
AU - Solanki, Abhishek
AU - Shore, Neal D.
AU - Guo, Gordon
AU - Ponsky, Lee
AU - Shoag, Jonathan E.
AU - Morgans, Alicia K.
AU - Garcia, Jorge A.
AU - Showalter, Timothy N.
AU - Feng, Felix Y.
AU - Spratt, Daniel E.
N1 - Funding Information:
Disclosures: Unless listed, no authors of conflicts of interest to report. D.E.S. reports personal fees from Varian, Janssen, Boston Scientific, AstraZeneca, Blue Earth, Bayer, and funding from Janssen. T.N.S. reports consulting fees from Myovant Sciences and research funding from Varian Medical Systems. N.G.Z. is supported by startup funding from Penn State Cancer Institute and Penn State College of Medicine. N.G.Z. is supported by the National Institutes of Health Grant LRP 1 L30 CA231572-01. N.G.Z. is supported by the American Cancer Society–Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG-20-013-01-CCE. N.G.Z. received remuneration from Springer Nature for his textbook, Absolute Clinical Radiation Oncology Review. N.G.Z. received payments from Weatherby Healthcare, unrelated to the present work. P.T. reports personal fees from Janssen, RefleXion, Myovant, AZ, Noxopharm, Tempus. Grants from Astellas, Bayer and RefleXion. Patent licensed to Natsar Pharm. A.K.M. reports Honoraria for consulting from Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Blue Earth, Clovis, Dendreon, Exelixis, Janssen, Myovant, Novartis, Pfizer, Sanofi, SeaGen, and research collaborations with Bayer, Dendreon, Myovant, Sanofi, and SeaGen. R.C. reports personal fees from Myovant, during the conduct of A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer (HERO) trial; personal fees from Abbvie, personal fees from Accuray, personal fees from Blue Earth, outside the submitted work. N.S. reports research/consulting fees from AbbVie, Ferring, Myovant, Pfizer, and Tolmar.
Funding Information:
Disclosures: Unless listed, no authors of conflicts of interest to report. D.E.S. reports personal fees from Varian, Janssen, Boston Scientific, AstraZeneca, Blue Earth, Bayer, and funding from Janssen. T.N.S. reports consulting fees from Myovant Sciences and research funding from Varian Medical Systems. N.G.Z. is supported by startup funding from Penn State Cancer Institute and Penn State College of Medicine. N.G.Z. is supported by the National Institutes of Health Grant LRP 1 L30 CA231572-01. N.G.Z. is supported by the American Cancer Society–Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG-20-013-01-CCE. N.G.Z. received remuneration from Springer Nature for his textbook, Absolute Clinical Radiation Oncology Review. N.G.Z. received payments from Weatherby Healthcare, unrelated to the present work. P.T. reports personal fees from Janssen, RefleXion, Myovant, AZ, Noxopharm, Tempus. Grants from Astellas, Bayer and RefleXion. Patent licensed to Natsar Pharm. A.K.M. reports Honoraria for consulting from Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Blue Earth, Clovis, Dendreon, Exelixis, Janssen, Myovant, Novartis, Pfizer, Sanofi, SeaGen, and research collaborations with Bayer, Dendreon, Myovant, Sanofi, and SeaGen. R.C. reports personal fees from Myovant, during the conduct of A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer (HERO) trial; personal fees from Abbvie, personal fees from Accuray, personal fees from Blue Earth, outside the submitted work. N.S. reports research/consulting fees from AbbVie, Ferring, Myovant, Pfizer, and Tolmar.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Androgen deprivation therapy (ADT) is an integral component in the management of prostate cancer across multiple disease states. Traditionally, luteinizing hormone-releasing hormone (LHRH) agonists constituted the backbone of ADT. However, gonadotropin-releasing hormone receptor hormone (GnRH) antagonists also are available, which offer faster testosterone suppression and reduced likelihood of ADT-related adverse effects compared with LHRH agonists, including the potential for fewer ADT-associated major cardiac events. Until recently, all forms of LHRH agonists and GnRH antagonist formulations were of parenteral administration. However, recently relugolix gained Food and Drug Administration approval as the first oral GnRH antagonist. Relugolix achieves faster and more complete testosterone suppression compared with an LHRH agonist. This translates to more rapid prostate-specific antigen response compared with LHRH agonists. After discontinuation of relugolix, testosterone recovers faster than after GnRH agonists or injectable GnRH antagonist therapy. Overall, these factors provide opportunities for more precisely defined ADT duration when combined with radiation therapy. The rapid onset and offset of testosterone suppression with relugolix may require physicians to rethink the mechanism and goals of ADT when prescribing. As an oral formulation, relugolix enables patients to avoid pain and injection site reactions, limit extra office visits for injections, and achieve a shorter duration of experiencing the side effects of castrate testosterone levels. This convenience and tolerability may enhance physicians’ willingness to prescribe ADT and patients’ feeling of control during their ADT course, but the potential advantages are accompanied by the risks of patients choosing to discontinue therapy to escape side effects of ADT. This article focuses on different aspects of what is known and unknown regarding the optimal use of ADT and radiation therapy, and how relugolix, due to its properties, fit into our current treatment paradigms for localized prostate cancer.
AB - Androgen deprivation therapy (ADT) is an integral component in the management of prostate cancer across multiple disease states. Traditionally, luteinizing hormone-releasing hormone (LHRH) agonists constituted the backbone of ADT. However, gonadotropin-releasing hormone receptor hormone (GnRH) antagonists also are available, which offer faster testosterone suppression and reduced likelihood of ADT-related adverse effects compared with LHRH agonists, including the potential for fewer ADT-associated major cardiac events. Until recently, all forms of LHRH agonists and GnRH antagonist formulations were of parenteral administration. However, recently relugolix gained Food and Drug Administration approval as the first oral GnRH antagonist. Relugolix achieves faster and more complete testosterone suppression compared with an LHRH agonist. This translates to more rapid prostate-specific antigen response compared with LHRH agonists. After discontinuation of relugolix, testosterone recovers faster than after GnRH agonists or injectable GnRH antagonist therapy. Overall, these factors provide opportunities for more precisely defined ADT duration when combined with radiation therapy. The rapid onset and offset of testosterone suppression with relugolix may require physicians to rethink the mechanism and goals of ADT when prescribing. As an oral formulation, relugolix enables patients to avoid pain and injection site reactions, limit extra office visits for injections, and achieve a shorter duration of experiencing the side effects of castrate testosterone levels. This convenience and tolerability may enhance physicians’ willingness to prescribe ADT and patients’ feeling of control during their ADT course, but the potential advantages are accompanied by the risks of patients choosing to discontinue therapy to escape side effects of ADT. This article focuses on different aspects of what is known and unknown regarding the optimal use of ADT and radiation therapy, and how relugolix, due to its properties, fit into our current treatment paradigms for localized prostate cancer.
UR - http://www.scopus.com/inward/record.url?scp=85123603947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123603947&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2021.12.005
DO - 10.1016/j.ijrobp.2021.12.005
M3 - Review article
C2 - 34923058
AN - SCOPUS:85123603947
SN - 0360-3016
VL - 113
SP - 278
EP - 289
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -