ASCO GU 2024: Radiographic Progression Without PSA Progression in Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Analysis from the ENZAMET Trial (ANZUP 1304)

(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25^th and 27^th was host to a prostate cancer poster session. Dr. Ian Davis presented the results of a post-hoc, retrospective analysis from the ENZAMET trial (ANZUP 1304) evaluating the incidence of radiographic progression, in the absence of PSA progression, in patients with metastatic hormone sensitive prostate cancer (mHSPC).

ENZAMET is an international, open-label, randomized, phase 3 trial across 83 sites in Australia, Canada, Ireland, New Zealand, the UK, and the USA that randomized mHSPC patients 1:1 to either testosterone suppression plus oral enzalutamide (160 mg daily) or a weaker standard oral non-steroidal antiandrogen (bicalutamide, nilutamide, or flutamide) until clinical disease progression or prohibitive toxicity. Concurrent use of docetaxel was permitted at the discretion of the treating physician (16% had prior docetaxel and 45% with planned use of early docetaxel). After a median follow-up of 68 months, this trial met its primary endpoint with the 5-year overall survival improved from 57% to 67% in the enzalutamide + testosterone suppression arm (HR: 0.70, 95% CI: 0.58 – 0.84, p<0.0001).¹

In this analysis, the ENZAMET dataset was analyzed using a multi-state Cox proportional hazards regression model, partitioning the clinical experience of participants into four states:

1. Event-free
2. Radiographic progression recorded without prior/concurrent evidence of confirmed PSA progression per protocol (radiographic progression 1^st)
3. Other progression (all other types of clinical progression events [PSA and treatment switch, excluding death])
4. Death

Overall, radiographic progression was observed in 34% of patients (388/1,125). Notably, radiographic progression in the absence of confirmed prior/concurrent PSA progression was observed in 10% of the entire cohort (114/1,125), which accounts for 29% of all radiographic ‘progressors’. Radiographic progression in the absence PSA progression occurred in similar proportions for those assigned enzalutamide versus a non-steroidal anti-androgen (NSAA). The baseline characteristics of the 114 participants with radiographic progression in the absence of PSA progression were similar to other participants in ENZAMET and were similar in the enzalutamide and non-steroidal anti-androgen groups.
Post-progression survival time was shorter for patients with radiographic progression 1^st, compared to those without radiographic progression 1^st in both the enzalutamide (HR: 1.66, 95% CI: 1.19 – 2.32, p=0.003) and NSAA groups (HR: 1.51, 95% CI: 1.08 – 2.10, p=0.015). The 5-year overall survival rates were 24% in the radiographic progression 1^st group, compared to 42% in those with other progression events.

Of those who had not progressed (495/1,125), with a median follow-up of 68 months, 10% had died of causes other than prostate cancer. As previously reported, enzalutamide prolonged overall survival in the whole trial cohort (N=1,125; HR: 0.70, 95% CI: 0.58 to 0.84, p<0.001).

Compared with NSAA, enzalutamide delayed both radiographic progression 1^st (HR: 0.66, 95% CI: 0.46 to 0.96, p=0.03) and other progression (HR: 0.37, 95% CI: 0.31 to 0.44, p<0.001).

Dr. Davis concluded that this post-hoc analysis of ENZAMET demonstrated that:

• Participants who had radiographic progression in the absence of prior/concurrent PSA progression had worse overall survival, and the frequency was ~10% on either NSAA or enzalutamide. Radiographic 1^st progression likely reflects worse disease biology and fewer effective treatment options for mCRPC.
• Enzalutamide reduced the hazards for, and delayed the times to, radiographic progression 1^st and other progression events.
• There are currently no baseline characteristics to help identify radiographic progression 1^st participants upfront. Molecular biological analyses are planned to help prospectively identify this unique group earlier.

Presented by: Ian D. Davis, PhD, FRACP, MBBS, FAChPM, Medical Oncology, Professor of Medicine, Head at Monash University Eastern Health Clinical School, Melbourne, Australia

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25^th – January 27^th, 2024

1. Sweeney CJ, Martin AJ, Stockler MR, et al. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): An international, open-label, randomized, phase 3 trial. Lancet Oncol. 2023;24(4):323-34.