touchONCOLOGY presents the top new clinical trial findings that are generating a buzz among prostate cancer experts. Here’s the latest from one of the leading global conferences in GU oncology: the 2025 ASCO Genitourinary Cancers Symposium (February 26–28, 2025, San Francisco, CA, USA).

ENZA-p (ANZUP 1901): LuPSMA plus ENZA in mCRPC (Abstract 17)^1,2
Updated results from the ENZA-p trial (ClinicalTrials.gov identifier: NCT04419402) demonstrated that adding [177Lu]Lu-PSMA-617 (LuPSMA) to enzalutamide (ENZA) as first-line treatment in patients with poor-risk, metastatic castration-resistant prostate cancer (mCRPC) showed improved overall survival (OS) and health-related quality of life (HRQL).1,2 With a median follow-up of 34 months, median OS was longer in the ENZA+LuPSMA group compared to ENZA alone (34 versus 26 months; hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.36–0.84; p=0.005). Deterioration-free survival at 12 months favoured ENZA+LuPSMA for overall health and quality of life (40% versus 13%; p<0.001) and physical function (38% versus 17%; p<0.001). Pain and fatigue scores were also improved in the ENZA+LuPSMA group. The frequency of self-rated xerostomia was higher with ENZA+LuPSMA (74% versus 57%; p=0.04). 

Final results from TALAPRO-2 (Cohort 1): TALA plus ENZA in mCRPC (Abstract LBA18)^3,4
The phase III TALAPRO-2 trial (ClinicalTrials.gov identifier: NCT03395197) assessed the efficacy of talazoparib (TALA) combined with ENZA versus placebo with ENZA as an initial treatment for patients with metastatic castration-resistant prostate cancer (mCRPC).^3,4 The study previously met its primary endpoint of improving radiographic progression-free survival (rPFS), which supported the FDA approval of TALA plus enzalutamide for patients with mCRPC and homologous recombination repair (HRR) deficiency. Final data showed a statistically significant improvement in OS in a broader mCRPC population, encompassing individuals with both HRR-deficient and HRR–non-deficient tumours. OS benefit was most pronounced in patients with HRR-deficient tumors (HR 0.549, 95% CI 0.364–0.826; p=0.0035). Radiographic progression-free survival (rPFS) also favored TALA + ENZA (median rPFS 33.1 versus 19.5 months; HR 0.667, 95% CI 0.551–0.807; p<0.0001). The most common grade ≥3 treatment-emergent adverse events (TEAEs) were anaemia (49%) and neutropenia (19%).

TALAPRO-2 Cohort 2: TALA lus ENZA in HRR-deficient mCRPC (Abstract LBA141)^4,5
Cohort 2 of TALAPRO-2, focused on patients with HRR-deficient mCRPC, showed a statistically significant OS benefit for TALA + ENZA over ENZA alone (median OS 45.1 versus 31.1 months; HR 0.622, 95% CI 0.475–0.814; p=0.0005). OS benefit was strongest in patients with BRCA1/2 alterations (HR 0.497, 95% CI 0.318–0.776; p=0.0017). rPFS remained favorable for TALA + ENZA (median 30.7 versus 12.3 months; HR 0.468, 95% CI 0.359–0.612; p<0.0001). TEAEs were consistent with prior reports, with anaemia (43%) and neutropenia (20%) being the most common grade 3–4 events.

STOPCAP: Meta-analysis of ARPIs in mHSPC (Abstract 20)⁶
A STOPCAP meta-analysis of individual participant data from five trials (LATITUDE, STAMPEDE A versus G, SWOG-1216, ENZAMET, and STAMPEDE) evaluated androgen receptor pathway inhibitors (ARPIs) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).⁶ ARPIs improved OS (HR 0.69, 95% CI 0.64–0.74) and progression-free survival (PFS) (HR 0.49, 95% CI 0.45–0.53). Younger age, higher body mass index (BMI), and lower metastatic burden were associated with a greater PFS benefit. Network meta-analysis (NMA) suggested that ARPIs may provide greater OS benefit than docetaxel (HR 0.85, 95% CI 0.70–1.03), but in high-volume, synchronous disease, ARPIs and docetaxel appeared similarly effective (HR 0.89, 95% CI 0.74–1.06).

Age-related Efficacy of DARO in the ARASENS trial (Abstract 143)^7,8
A subgroup analysis of the ARASENS trial (ClinicalTrials.gov identifier: NCT02799602) examined the efficacy and safety of darolutamide (DARO) plus androgen deprivation therapy (ADT) and docetaxel (DOC) in patients with mHSPC stratified by age (<75 years versus ≥75 years).^7,8 Among 1,305 patients, the OS benefit of DARO versus placebo was consistent across age groups (<75 years: HR 0.70, 95% CI 0.58-0.84; ≥75 years: HR 0.61, 95% CI 0.41–0.91). DARO also extended time to mCRPC (<75 years: HR 0.35, 95% CI 0.30-0.43; ≥75 years: HR 0.42, 95% CI 0.28–0.64) and delayed initiation of subsequent therapy. TEAEs were generally comparable between treatment groups, with slightly higher rates in older patients. Treatment discontinuation rates due to TEAEs were low in both age subgroups.

Disease volume and DARO efficacy in the ARANOTE trial (Abstract 151)^9,10
The ARANOTE trial (ClinicalTrials.gov identifier: NCT04736199) evaluated the impact of disease volume on treatment efficacy of DARO plus ADT in patients with mHSPC.^9,10 Of 669 patients, 71% had high-volume (HV) disease and 29% had low-volume (LV) disease. DARO reduced the risk of radiological progression or death by 70% in patients with LV disease (HR 0.30, 95% CI 0.15–0.60) and by 40% in patients with HV disease (HR 0.60, 95% CI 0.44–0.80). Time to mCRPC and PSA progression were also significantly improved in both subgroups. The safety profile was favourable, with low incidences of TEAEs and lower rates of treatment discontinuation in patients with LV disease.

References

1. Emmett L, Subramaniam S, Crumbaker M, et al. Overall survival and quality of life with [177Lu] Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901). J Clin Oncol. 2025;43(Suppl.5):Abstr17.
2. ClinicalTrials.gov. Enzalutamide With Lu PSMA-617 Versus Enzalutamide Alone in Men With Metastatic Castration-resistant Prostate Cancer (ENZA-p). ClinicalTrials.gov identifier: NCT04419402. Available at: https://clinicaltrials.gov/study/NCT04419402 (accessed 27 February 2025).
3. Agarwal N, Azad A, Carles J, et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. J Clin Oncol. 2025;43(Suppl.5):AbstrLBA18.
4. ClinicalTrials.gov. Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC (TALAPRO-2). ClinicalTrials.gov identifier: NCT03395197. Available at: https://clinicaltrials.gov/study/NCT03395197 (accessed 27 February 2025).
5. Fizazi K, Azad A, Matsubara N, et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line (1L) treatment in patients (pts) with homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. J Clin Oncol. 2025;43(Suppl.5):AbstrLBA141.
6. Fisher D, Vale C, Rydzewska K, et al. Which patients with metastatic hormone-sensitive prostate cancer (mHSPC) benefit more from androgen receptor pathway inhibitors (ARPIs)? STOPCAP meta-analyses of individual participant data (IPD). J Clin Oncol. 2025;43(Suppl.5):Abstr20.
7. Carles J, Tombal B, Hussain M, et al. Age-related efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) and docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC): A subgroup analysis of ARASENS. J Clin Oncol. 2025;43(Suppl.5):Abstr143.
8. ClinicalTrials.gov. Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer (ARASENS). ClinicalTrials.gov identifier: NCT02799602. Available at: https://clinicaltrials.gov/study/NCT02799602 (accessed 27 February 2025).
9. Saad F, Shore N, Vjaters E, et al. Darolutamide plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC) by disease volume: Subgroup analysis of the phase 3 ARANOTE trial. J Clin Oncol. 2025;43(Suppl.5):Abstr151.
10. ClinicalTrials.gov. Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE). ClinicalTrials.gov identifier: NCT04736199. Available at: https://clinicaltrials.gov/study/NCT04736199 (accessed 27 February 2025).

Disclosures: This article was created by the touchONCOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.

Cite: ASCO GU25: Highlights in Prostate Cancer. touchONCOLOGY. March 4th, 2025

 

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