Top Line: Does swapping an LHRH agonist (e.g. leuprolide) for an antagonist (e.g., degarelix) improve outcomes when paired with radiation for very high-risk prostate cancer?
The Study: You first may ask: why would it? “Unlike LHRH agonists, the LHRH antagonist degarelix immediately suppresses the secretion of testosterone, and thus an initial surge of testosterone is avoided.” EORTC 1414 is the first randomized trial to pit long-course degarelix against standard LHRH agonists in men receiving radiation for very high-risk prostate cancer, including a small oligometastatic subset. The original primary endpoint of progression-free survival was abandoned after slow accrual (379 enrollees of 670 planned). Instead, the new target was a PSA nadir <0.1 ng/mL within 6 months of completing radiation, which was not significantly different between the smaller-than-hoped arms: 60% with agonists and 52% with degarelix. Two-year progress-free survival was indistinguishable at 88%. As hoped, among patients with baseline cardiovascular disease, cardiac events were uncommon and numerically less with degarelix (n=1) than LHRH agonists (n=4). Degarelix also produced modestly better urinary symptom improvement in those starting with worse urinary function.
TBL: Degarelix didn’t deliver a deeper PSA response or better short-term progression-free survival, but may offer meaningful cardiac and urinary advantages for select high-risk patients. | Zilli, Eur Urol Oncol 2025
The Study: You first may ask: why would it? “Unlike LHRH agonists, the LHRH antagonist degarelix immediately suppresses the secretion of testosterone, and thus an initial surge of testosterone is avoided.” EORTC 1414 is the first randomized trial to pit long-course degarelix against standard LHRH agonists in men receiving radiation for very high-risk prostate cancer, including a small oligometastatic subset. The original primary endpoint of progression-free survival was abandoned after slow accrual (379 enrollees of 670 planned). Instead, the new target was a PSA nadir <0.1 ng/mL within 6 months of completing radiation, which was not significantly different between the smaller-than-hoped arms: 60% with agonists and 52% with degarelix. Two-year progress-free survival was indistinguishable at 88%. As hoped, among patients with baseline cardiovascular disease, cardiac events were uncommon and numerically less with degarelix (n=1) than LHRH agonists (n=4). Degarelix also produced modestly better urinary symptom improvement in those starting with worse urinary function.
TBL: Degarelix didn’t deliver a deeper PSA response or better short-term progression-free survival, but may offer meaningful cardiac and urinary advantages for select high-risk patients. | Zilli, Eur Urol Oncol 2025