KEY TAKEAWAYS
- The ENZAMET phase 3 trial aimed to investigate the impact of enzalutamide, focusing on radiographic progression without PSA in mHSPC.
- Researchers observed worse overall survival in mHSPC participants with radiographic progression without prior PSA progression.
ENZAMET, a randomized trial comparing enzalutamide (ENZA) to a standard non-steroidal anti-androgen (NSAA) in 1125 metastatic hormone-sensitive prostate cancer (mHSPC) participants, demonstrated superior PFS and OS with ENZA. Radiographic progression without prior/concurrent PSA progression (rProg1st) is an emerging biomarker of poor clinical outcomes. Ian D. Davis and his team aimed to determine its frequency and assess enzalutamide’s impact on disease state transition for the ENZAMET cohort.
Researchers used a multi-state Cox proportional hazards regression model to perform an inclusive analysis on the ENZAMET dataset. This model categorized participants into four states: (1) Evt-Free (event-free), (2) rProg1st (radiologic progression without confirmed PSA progression), (3) OtherProg (All Other types of clinical progression events (PSA and treatment switch, excluding death), (4) Death.
Radiographic progression was documented in 34% (388/1125) of participants, with 10% (114/1125) experiencing radiographic progression without confirmed prior/concurrent PSA progression according to the protocol. Among them, 48% (55/114) were assigned ENZA and 52% (59/114) NSAA. Baseline characteristics of the 114 participants with rProg1st were comparable to the overall ENZAMET cohort and showed no significant differences between ENZA and NSAA groups. ENZA exhibited a delay in both rProg1st (HR 0.66, 95%CI: 0.46 to 0.96, P=0.03) and OtherProg (HR 0.37, 95%CI: 0.31 to 0.44, p<0.001) compared to NSAA. The 5-year OS rates were 24% (95%CI: 18-34) in the rProg1st group versus 42% (95%CI: 38-47) in the OtherProg group. Among those who had not progressed (495/1125) with a median follow-up of 68 months, 8% died from causes unrelated to prostate cancer. As previously reported, ENZA extended overall survival in the entire trial cohort (N=1125, HR 0.70, 95%CI 0.58 to 0.84, P<0.0001).
The study concluded that participants experiencing radiographic progression without prior/concurrent PSA progression demonstrated worse overall survival, irrespective of NSAA or enzalutamide assignment. Enzalutamide significantly reduced hazards and delayed the onset of both rProg1st and OtherProg. Despite the absence of identifiable baseline characteristics, the study advocates for future molecular biological analyses to facilitate early identification of this unique subgroup.
The Study is sponsored by University of Sydney
Source: https://meetings.asco.org/abstracts-presentations/230122
Clinical Trail: https://clinicaltrials.gov/study/NCT02446405
Davis. I D, Martin A J, Zielinski R R, et.al (2024). “Radiographic progression without PSA progression in metastatic hormone-sensitive prostate cancer (mHSPC): A retrospective analysis from the ENZAMET trial (ANZUP 1304).” Presented at ASCO GU 2024 (Abstract 151).
