365 - Relugolix vs. Leuprolide in Combination with Radiotherapy for Localized Prostate Cancer: Analysis of Patient-Reported Quality of Life in a Randomized Trial

09:55am - 10:05am ET

Room 253

Presenter(s)

Nikhil Sebastian, MD - Emory University Winship Cancer Institute, Atlanta, GA

N. Sebastian¹, B. Zheng², S. Goyal³, Y. Liu⁴, V. R. Dhere⁵, B. Hershatter⁵, P. R. Patel⁵, M. G. Sanda⁶, A. Jani⁷, and S. A. Patel⁷; ¹Emory Proton Therapy Center, Atlanta, OH, ²Emory University, Atlanta, GA, ³Department of Biostatistics and Bioinformatics Shared Resource, Winship Cancer Institute of Emory University, Atlanta, GA, ⁴Department of Biostatistics and Bioinformatics, Emory Winship Cancer Institute, Atlanta, GA, ⁵Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ⁶Department of Urology, Emory University School of Medicine, Atlanta, GA, ⁷Department of Radiation Oncology, Emory University, Atlanta, GA

Purpose/Objective(s):

Relugolix, a novel oral gonadotropin releasing hormone (GnRH) antagonist, improves testosterone kinetics, including rapid and more profound suppression with faster recovery after discontinuation, versus GnRH agonists. In a secondary analysis of a randomized trial of men receiving radiotherapy (RT) with concomitant androgen deprivation therapy (ADT) for localized prostate cancer (REVELUTION; NCT05320406), we compared longitudinal patient-reported outcomes (PROs) between GnRH-antagonist relugolix versus GnRH-agonist leuprolide.

Materials/Methods:

Men with localized prostate cancer planned for pelvic RT with concomitant ADT of = 6 months duration were randomized 1:1 to receive either leuprolide or relugolix with RT and stratified by Atherosclerotic Cardiovascular Disease (ASCVD) risk. International Prostate Symptom Score (IPSS), Expanded Prostate cancer Index Composite for Clinical Practice (EPIC-CP), and Sexual Health Inventory for Men (SHIM) questionnaires, as well as serum testosterone levels, were collected at baseline and 3, 6, and 12 months following treatment ADT initiation. PROs were analyzed using multivariable linear mixed effects models accounting for treatment arm, time, and their interaction, adjusted for baseline age, prostate gland volume, elective nodal irradiation, and receipt of a brachytherapy boost.

Results:

Sixty-five men were randomized and received either leuprolide (n = 34) or relugolix (n = 31) with RT from June 2022 to May 2023. Most patients received 6 months of ADT (leuprolide, n = 24; relugolix, n = 20) versus 12+ months, with a median time from ADT initiation to RT start of 4.3 weeks in both groups. Most patients in each group received prostate plus elective pelvic lymph node radiation (leuprolide, n = 19; relugolix, n = 22). Mean (± standard error) testosterone levels were similar between groups at baseline (292.8±15.1 vs 254.5±15.8 ng/dL; p = 0.08), 3 months (37.5±10.3 vs 26.5±7.3 ng/dL; p = 0.30), and 6 months (31.1±8.0 vs 25.5±5.3 ng/dL; p = 0.88), but were higher with relugolix at 12 months (199.7±16.6 vs 142.0±18.5 ng/dL; p = 0.01). There were no significant differences in IPSS, EPIC-CP, or SHIM at baseline or month 3 and 6. At month 12, relugolix, versus leuprolide, was associated with lower IPSS (5.66±1.22 versus 9.22±1.20; p = 0.039), EPIC-CP total (12.25±1.57 versus 17.25±1.56; p = 0.02), EPIC-CP bowel (0.35±0.41 versus 2.14±0.41; p = 0.003), and EPIC-CP vitality (1.80±0.49 vs 3.16 ± 0.50; p = 0.05) scores. There was no significant difference in EPIC-CP incontinence (p = 0.32), EPIC-CP urinary irritation (p = 0.15), EPIC-CP sexual (p = 0.56), or SHIM (p = 0.92) scores at 12 months.

Conclusion:

In men receiving definitive RT plus ADT for localized prostate cancer, relugolix results in comparable short-term testosterone suppression with faster recovery and improved obstructive urinary, bowel, and vitality quality-of-life measures at 12 months versus leuprolide. These findings are exploratory and support prospective validation.