Short-course (3-month) enzalutamide monotherapy in biochemically recurrent prostate cancer (BCR): Preliminary prostate specific membrane antigen tumor volume (PSMA-TV) data.

23 Background: Enzalutamide (enza) monotherapy is a treatment option for BCR. Although EMBARK evaluated 9 months of enza monotherapy, a previous study (n=38) at the National Cancer Institute (NCI) evaluated two 3-month intermittent courses of enza without androgen deprivation (ADT). The results indicated that PSA control (disease below PSA baseline) was a median of 308 days with 3 months of enza for course 1 and 273 days for course 2, emphasizing a therapeutic approach focused on treatment free survival. No patients (pts) had progression on CT or bone scan after PSA recovery to baseline PSA after 3 months of enza for up to 2 intermittent courses. (Madan, RA et al., JITC, 2021). Although prostate specific membrane antigen (PSMA) scans are increasingly being used for response assessment in prostate cancer with presumed informative potential, it remains unknown how most therapies including enza monotherapy will impact PSMA-TV. PSMA-TV has been proposed as key PSMA readout (e.g. RECIP 1.0) but has rarely been prospectively evaluated in therapeutic trials to date. Methods: NCT06096870 is a clinical trial (n=50) at the NCI randomizing BCR pts to either enza monotherapy or enza + PDS01ADC (IL-12 immunocytokine). Pts must have negative CT, bone scan, T>100, and PSMA+ BCR. All pts are treated with enza for 3 months without ADT. PSMA scans are done at baseline and after 3 months of enza. Upon PSA recovery to baseline, all pts are eligible for another course of 3 months of enza if CT and bone scan remain negative. This analysis evaluates the first group of pts who had enza monotherapy only with paired PSMA before/after enza. Baseline PSMA-TV was compared with PSA response data after 3 months of enza. Results: Among the first 13 enza monotherapy pts, medians were age=71 years, PSA=22.5 ng/ml, PSA doubling time=3.5 months, PSMA-TV=11.1 milliliters. Median PSA response was -98% (-81% to -100%) for a duration of 259 days (including only 84 days of enza). The median PSMA-TV response was -71.7% (+13.2% to -100%). Of note, among 4 pts with PSA=0 ng/ml after enza, PSMA-TV=0 in 2 pts, PSMA-TV= -86% in a 3 rd pt but PSMA-TV= +2.8% in the 4 th pt. Furthermore, the PSMA TV increase in 4 th pt did not predict poor clinical response and that pt even had longer PSA control than a pt with a 100% PSA decline and complete response on PSMA. Conclusions: This is the first data presented evaluating PSMA-TV changes after enza in BCR without ADT. Despite this small data set, lack of concordance of PSA and PSMA responses should highlight a need to collect more data to better understand the clinical utility of PSMA scans in defining therapeutic response in BCR. It further indicates the need for caution in the use of PSMA imaging presumptively to define therapeutic benefit or lack thereof in clinical practice. Clinical trial information: NCT06096870 .