Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with 177Lu-PSMA-617 for metastatic Castration-reSISTant Prostate Cancer (RESIST-PC): Efficacy results of the UCLA cohort.

Objective: To determine prospectively the efficacy profile of 2 activity regimens of Lu-PSMA therapy in patients with progressive metastatic castrate resistant prostate cancer (mCRPC): 6.0 vs 7.4 GBq.

Methods: RESIST-PC (NCT03042312) was a prospective multicenter phase 2 trial. Patients with progressive mCRPC after ≥1 novel androgen-axis drug, either chemotherapy naïve or post-chemotherapy, with sufficient bone marrow reserve, normal kidney function, and sufficient PSMA expression by PSMA PET were eligible. Patients were randomized (1:1) into two activity groups (6.0 or 7.4 GBq) and received up to 4 cycles every 8 weeks. The primary endpoint was the efficacy of Lu-PSMA measured by the PSA response rate (RR) after 2 cycles (≥50% decline from baseline). Secondary endpoints included the PSA-RR (≥50% decline) at any time (best response), and overall survival (OS). Results: The study was closed at enrollment of 71/200 planned patients because of sponsorship transfer. We report here the efficacy UCLA cohort results only (n = 43). The PSARRs after 2 cycles and at any time were 11/40 (28%, 95%CI 15-44), 6/13 (46%, 95%CI 19-75), 5/27 (19%, 95%CI 6-38), and 16/43 (37%, 95%CI 23-53), 7/14 (50%, 95%CI 23-77), 9/29 (31%, 95%CI 15-51) in the whole cohort, the 6.0 GBq and the 7.4 GBq groups, respectively (P = 0.12 and P = 0.31). The median OS was 14.0 months (95%CI 10.1-17.9), 15.8 (95%CI 11.8-19.4), 13.5 (95%CI 10.0-17.0) in the whole cohort, the 6.0 GBq and the 7.4 GBq groups, respectively (P = 0.87). OS was longer in patients who experienced a PSA decline ≥50% at any time than those who did not: median: 20.8 vs. 10.8 months (P = 0.005). Conclusion: In this prospective phase 2 trial of Lu-PSMA for mCRPC the median OS was 14 months. Despite the heterogeneous study population and the premature study termination, the efficacy profile of Lu-PSMA appeared to be favorable and comparable with both activity regimens (6.0 GBq vs. 7.4 GBq). Results justify confirmation with real world data matched pair analysis and further clinical trials to refine and optimize the LuPSMA therapy administration scheme to improve tumor radiation dose delivery and efficacy.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2021 May 20 [Epub ahead of print]

Jeremie Calais, Andrei Gafita, Matthias Robert Eiber, Wesley Robert Armstrong, Jeannine Gartmann, Pan Thin, Kathleen Nguyen, Vincent Lok, Laura Gosa, Tristan Grogan, Rouzbeh Esfandiari, David Ranganathan, Martin S Allen-Auerbach, Andrew Quon, Shadfar Bahri, Pawan Gupta, Linda Gardner, Roger Slavik, Magnus Dahlbom, Ken Herrmann, Ebrahim S Delpassand, Wolfgang Peter Fendler, Johannes Czernin

UCLA, United States., Nuclear Medicine, TU Munich., Excel Diagnostics & Nuclear Oncology Center., Radiomedix., UCLA SCHOOL OF MEDICINE., UCLA School of Medicine., Essen University Hospital.