Radium 223 without androgen deprivation therapy (ADT) in patients (Pts) with biochemically recurrent prostate cancer (BCR) and PET findings in the bones.

192 Background: BCR pts have a rising PSA after definitive surgery or radiation, but negative CT/Tc-99m bone scans. While ADT-based strategies are commonly used, they can be associated with life-altering toxicities. Radium-223 is an alpha-emitting radiopharmaceutical that accumulates in areas of high bone turnover and has demonstrated a survival benefit in metastatic prostate cancer but its benefits as a monotherapy in BCR without ADT have not been explored prior to this study. This strategy may be important as bone metastasis drives morbidity/mortality in prostate cancer. Methods: Eligible pts in this study (NCT04206319) have BCR following definitive therapy, testosterone (T) >100ng/dL, normal organ and marrow function, and negative CT/Tc-99m bone imaging. Pts must have findings on NaF or PSMA PET suspicious for metastatic bone disease not seen on Tc-99m bone scan. Pts are treated with Radium-223 at the approved dosing of 55 kBq/kg for 6 cycles. PSA declines were defined as 2 or more confirmed declines from an intra-study apex PSA (ISAP; Madan ASCO GU 2018). All pts have pre- and post-treatment PSMA and NaF imaging. Immune responses (primary endpoint) are to be evaluated at study completion. Results: 25 pts have enrolled with 24 currently evaluable for response, with a median age of 69 yrs (57-80) and PSA of 1.75 ng/ml (0.2-49.5). 21/24 pts had PSMA+ scans. 21/24 pts had NaF+ scans. Grade 2 toxicities have been rare and no grade 2 changes in hemoglobin or platelets have occurred. There have been no grade 3/4 toxicities and no cycles missed for toxicity. Two pts with rapid PSA doubling times came off study early for progression and were not evaluable for follow up imaging. 8/24 pts (33%) had confirmed ISAP PSA declines of 12% to 80% lasting from 84 to 682 days, with two ongoing PSA responses. Delayed PSA responses following completion of treatment were observed. 13/21 evaluable pts had evidence of decreased maximum standardized uptake value (SUVmax) on NaF PET imaging after treatment. 5/19 evaluable patients with PSMA PET+ lesions had a radiographic response; two pts had resolution of multiple PSMA+ bone findings, one of whom remains with negative bone findings on PET after 2+ years and with a stable PSA. Conclusions: Radium-223 in BCR is safe and associated with minimal grade 1/2 toxicities. Decreases in SUVmax seen on most NaF scans suggest Radium-223 targeting of suspicious lesions. Improvements in PSMA imaging have been observed. Delayed but confirmed PSA declines have been seen in 33% of pts. Radium-223 monotherapy may have therapeutic activity in BCR and further studies are needed to define its potential role in BCR in patients with PET+ bone findings. Clinical trial information: NCT04206319 .