Intensified hormonal blockade with SBRT in PSMA-PET detected oligometastatic prostate adenocarcinoma: Results from the phase II Metacure trial cohorts B2 and the B2 expansion.

5014 Background: Metastasis directed therapy (MDT) with stereotactic body radiotherapy (SBRT) is a standard of care in patients with oligometastatic hormone-sensitive prostate cancer (HSPC) and can delay the use of ADT. Combining SBRT with a defined period of systemic therapy may lead to durable control of oligometastatic disease and is often used in this setting, however the optimal intensity and duration of hormonal blockade with SBRT remains unclear. Methods: Metacure is a multi-center, multi-arm randomized phase 2 trial that tests novel systemic therapies in the context of a multimodality approach, including SBRT to oligometastatic sites. The B2 and B2 expansion cohorts of Metacure tested SBRT +/- salvage RT to prostate bed/nodes with time-limited ADT+ARPI hormonal blockade in patients (pts) with PSMA-PET detected metachronous oligometastatic HSPC. Eligible pts had biochemical recurrence or persistence (PSA >0.2) after prostatectomy with metastases treatable within max 3 RT plans. Cohort B2 randomized pts to metastasis-directed SBRT with either 10 months of ADT + apalutamide + abiraterone acetate plus prednisone (ADT+APA+AAP) or ADT + apalutamide (ADT+APA). In the B2 expansion cohort pts received 6 months of ADT+APA with SBRT. The primary endpoint was proportion of pts with undetectable PSA (PSA<0.1) at 12 months from treatment start in pts with recovered testosterone (T). Secondary objectives included PSA<0.1 at 24 months, time to PSA progression (PSA 0.2), time to T recovery, rPFS, and PFS (PSA, radiographic, or clinical progression or death). Results: 36 pts were treated in the combined B2 (10 pts) and B2 expansion (26 pts) cohorts. Median follow-up was 35 months for cohort B2 and 19 months for the B2 expansion. T recovery (>150ng/dl) at 12 months from treatment start occurred in 3/5 (60%) ADT+APA+AAP and 2/5 (40%) ADT+APA pts on cohort B2 and 14/26 pts (54%) on the B2 expansion (ADT+APA). Of those, 2/2 (100%) B2 ADT+APA+AAP pts, 3/3 (100%) B2 ADT+APA and 11/14 (79%) B2 expansion pts had PSA <0.1. This met the pre-specified threshold for activity for the B2 expansion of 4 pts. Median time to PSA progression and PFS was 26 months for the B2 ADT+APA+AAP arm and not reached for the B2 ADT+APA arm or B2 expansion cohort. Median rPFS was not reached in any group. At 12 months, all patients on B2 and B2 expansion were progression free. At 18 months, PFS for B2 was 100% (ADT+APA) and 60% (ADT+APA+AAP) and was 85% for the B2 expansion. At 24 months, PFS was 60% for ADT+APA and 60% for ADT+APA+AAP pts on cohort B2. Median T recovery was 3.0 and 5.5 months for the B2 and B2 expansion cohorts. Grade 3 TRAEs were seen in 0/10 B2 and 1/26 B2 expansion subjects (lymphopenia). Conclusions: SBRT with short course intensified hormonal blockade was well tolerated and led to durable disease control in pts with PSMA PET-detected metachronous oligometastatic prostate cancer. Clinical trial information: NCT03436654 .