Ursula Vogl presented key highlights from ESMO 2024 focusing on prostate cancer, covering advancements across different disease stages. The discussion included the PATCH trial on transdermal estradiol, the ARANOTE trial on darolutamide, the PEACE-3 trial on radium-223 plus enzalutamide, and the STAMPEDE trial's findings on metformin.
Transdermal Estradiol vs. LHRH Analogs in Non-Metastatic Prostate Cancer
The PATCH trial, combined with data from a STAMPEDE arm, investigated transdermal estradiol as an alternative to LHRH analogs in non-metastatic prostate cancer. The rationale behind this approach is that transdermal estradiol maintains estradiol levels while suppressing testosterone, potentially reducing adverse events like osteoporosis and lipid changes associated with LHRH analogs. The trial, involving over 1,000 patients, demonstrated non-inferiority in metastasis-free survival (MFS) with a three-year MFS rate of 87% in both arms. Overall survival was also non-inferior. While hot flashes were less frequent with transdermal estradiol, gynecomastia was more common (43% higher). Professor Langley suggested that transdermal estradiol patches could be a standard of care option in M0 disease, but questions remain regarding its use in metastatic disease and long-term metabolic benefits.
Darolutamide in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
The ARANOTE trial, a phase III study, evaluated the addition of darolutamide to ADT in metastatic hormone-sensitive prostate cancer. The primary endpoint, rPFS, was met with a hazard ratio of 0.5. While overall survival data is still immature, a trend favoring the darolutamide arm was observed. Notably, darolutamide showed a favorable safety profile, with treatment-related adverse events similar to placebo plus ADT. However, bone fractures were more frequent with darolutamide. Fred Saad suggested darolutamide and ADT as a new standard of care for mHSPC, pending overall survival results and regulatory approvals.
Metformin's Impact on Prostate Cancer
The STAMPEDE RMK trial assessed the benefit of metformin added to standard of care in prostate cancer. The trial, involving 1,874 patients, did not meet its primary endpoint of overall survival. However, subgroup analysis suggested a potential benefit in high-volume patients. Metformin significantly improved metabolic parameters, such as weight gain, cholesterol, and glucose levels. While metformin did not improve overall survival, it may have a role in managing metabolic adverse events associated with hormonal treatments.
Radium-223 Plus Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
The PEACE-3 trial investigated the combination of Radium-223 plus enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer with bone metastases. The primary endpoint, rPFS, was met with a significant hazard ratio. Overall survival at interim analysis favored the combination, but statistical significance was not yet reached. The combination was well-tolerated, although anemia and neutropenia were more common with the addition of radium-223. Professor Gillessen suggested this combination as a potential new standard of care in first-line mCRPC patients with predominant bone metastasis.
Lutetium PSMA Therapy
The SPLASH phase III trial presented by Professor Sartor was also a topic at the ESMO meeting. The trial studied lutetium PSMA-I&T in mCRPC. The study reached its primary endpoint with rPFS. OS is immature, and it has a good profile. Irene Burger discussed the SPLASH trial and the open questions, especially about optimal dosing and timing of lutetium PSMA therapies since we have two different products actually available.
