1819P - PSMA-BAT: Prospective biomarker trial of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) undergoing bipolar androgen therapy (BAT)

Background

BAT has shown clinical activity and capacity of tumor resensitization to androgen receptor targeted therapy in mCRPC. We aimed to explore imaging and genomic biomarkers of response to BAT.

Methods

This is a single-arm study of pts with mCRPC and progressive disease on at least one novel AR-targeted therapy. Pts were treated with BAT (testosterone cypionate 400 mg intramuscular) every 4 weeks. All pts underwent PSMA-PET/CT (PSMA-PET) and FDG-PET/CT (FDG-PET) at baseline and week 12. Molecular tumor volume (mTV), total lesion expression (TL), standardized uptake value (SUV) max and mean were evaluated in PSMA-PET scans; total lesion glycolisys (TLG), metabolic tumor volume (MTV), SUVmax and SUVmean in FDG-PET scans. AR-V7 expression in circulating tumors cells (CTCs) was analyzed in each cycle and at week 12. Variables were correlated with PSA response, 6-month progression-free survival (PFS) and overall survival (OS).

Results

A total of 20 pts were included from Oct 2020 to Mar, 2022. Median age was 66y, and median number of prior systemic therapies was 3.5 (2-5). Any PSA and PSA50 responses were achieved in 45% and 30% of pts. Median PFS was 5.6 months (mos) (95% CI 3.4 - 7.8 mos), and 40% reached a PFS >6 mos. PFS or OS were not associated with baseline PSA or demographic characteristics. Higher interim PSMA mTV, variation (Δ) mTV week 12-baseline mTV > -17%, Δ TL-PSMA week 12-baseline >39% and higher week 12 PSA/PSMA SUVmax were associated with PFS < 6 mos (p=0.01; p=0.009; p=0.009, p=0.01). Median OS was 23.1 mos. Higher baseline PSMA mTV, TL-PSMA, FDG MTV and TLG were associated with worse OS (p=0.009; p=0.02; p=0.006; p=0.02). At baseline, 14/20 pts were positive (+) for CTCs. Of those, 8 were AR-V7+. At week 12, 6 pts became negative (-) for CTCs and 6 became - for AR-V7; only 2 pts became + for CTCs and none became + for AR-V7. The difference between baseline and week 12 AR-V7 + pts was statistically significant (p=0.03). Positive AR-V7 was associated with worse OS (p<0.05).

Conclusions

Higher PSMA-PET mTV and TL-PSMA may predict worse PFS in pts treated with BAT. Positive AR-V7 was associated with worse OS. Responses to BAT can influence AR-V7 dynamics. Larger trials are necessary to confirm our findings.

Clinical trial identification

NCT04424654.

Editorial acknowledgement

Legal entity responsible for the study

Hospital Sírio-Libanês.

Funding

Ludwig Cancer Research and Hospital Sírio-Libanês.

Disclosure

A.B. Lara Gongora: Financial Interests, Invited Speaker, Travel, Accommodations, Expenses: Bayer, Astellas, Janssen, MSD, AstraZeneca. D.L.F. Jardim: Financial Interests, Invited Speaker, Speaker/scientific support for events: Astellas; Financial Interests, Invited Speaker, Speaker/Scientific support for events: Janssen, BMS; Financial Interests, Advisory Board: Janssen, Libbs; Financial Interests, Sponsor/Funding, Scientific support for events: Roche; Financial Interests, Invited Speaker: Libbs, MSD; Financial Interests, Writing Engagements: Libbs; Financial Interests, Funding, Research Funding: Recepta. G.B. Grossman: Financial Interests, Invited Speaker, Speaker/Consultant: Pfizer, Siemens. D.A. Bastos: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Invited Speaker: BMS, Janssen, Astellas, AstraZeneca, Bayer. All other authors have declared no conflicts of interest.