TY - JOUR T1 - Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with <sup>177</sup>Lu-PSMA-617 for metastatic Castration-reSISTant Prostate Cancer (RESIST-PC): Efficacy results of the UCLA cohort JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.121.261982 SP - jnumed.121.261982 AU - Jeremie Calais AU - Andrei Gafita AU - Matthias Robert Eiber AU - Wesley Robert Armstrong AU - Jeannine Gartmann AU - Pan Thin AU - Kathleen Nguyen AU - Vincent Lok AU - Laura Gosa AU - Tristan Grogan AU - Rouzbeh Esfandiari AU - David Ranganathan AU - Martin S Allen-Auerbach AU - Andrew Quon AU - Shadfar Bahri AU - Pawan Gupta AU - Linda Gardner AU - Roger Slavik AU - Magnus Dahlbom AU - Ken Herrmann AU - Ebrahim S. Delpassand AU - Wolfgang Peter Fendler AU - Johannes Czernin Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/early/2021/05/20/jnumed.121.261982.abstract N2 - 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. ER -