RT Journal Article SR Electronic T1 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 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1440 OP 1446 DO 10.2967/jnumed.121.261982 VO 62 IS 10 A1 Calais, Jeremie A1 Gafita, Andrei A1 Eiber, Matthias A1 Armstrong, Wesley R. A1 Gartmann, Jeannine A1 Thin, Pan A1 Nguyen, Kathleen A1 Lok, Vincent A1 Gosa, Laura A1 Grogan, Tristan A1 Esfandiari, Rouzbeh A1 Allen-Auerbach, Martin A1 Quon, Andrew A1 Bahri, Shadfar A1 Gupta, Pawan A1 Gardner, Linda A1 Ranganathan, David A1 Slavik, Roger A1 Dahlbom, Magnus A1 Herrmann, Ken A1 Delpassand, Ebrahim A1 Fendler, Wolfgang P. A1 Czernin, Johannes YR 2021 UL http://jnm.snmjournals.org/content/62/10/1440.abstract AB The objective of this study was to determine prospectively the efficacy profile of 2 activity regimens of 177Lu-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 postchemotherapy, with sufficient bone marrow reserve, normal kidney function, and sufficient PSMA expression by PSMA PET were eligible. Patients were randomized (1:1) into 2 activity groups (6.0 or 7.4 GBq) and received up to 4 cycles every 8 wk. The primary endpoint was the efficacy of 177Lu-PSMA measured by the prostate-specific antigen (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 of the University of California Los Angeles cohort results only (n = 43). The PSA RRs after 2 cycles and at any time were 11/40 (28%, 95% CI 15–44), 6/13 (46%, 95% CI 19–75), and 5/27 (19%, 95% CI 6–38), and 16/43 (37%, 95% CI 23–53), 7/14 (50%, 95% CI 23–77), and 9/29 (31%, 95% CI 15–51) in the whole cohort, the 6.0-GBq group, and the 7.4-GBq group, respectively (P = 0.12 and P = 0.31). The median OS was 14.0 mo (95% CI 10.1–17.9), 15.8 (95% CI 11.8–19.4), and 13.5 (95% CI 10.0–17.0) in the whole cohort, the 6.0-GBq group, and the 7.4 GBq group, respectively (P = 0.87). OS was longer in patients who experienced a PSA decline ≥ 50% at any time than in those who did not: median, 20.8 versus 10.8 mo (P = 0.005). Conclusion: In this prospective phase 2 trial of 177Lu-PSMA for mCRPC, the median OS was 14 mo. Despite the heterogeneous study population and the premature study termination, the efficacy profile of 177Lu-PSMA appeared to be favorable and comparable with both activity regimens (6.0 vs. 7.4 GBq). Results justify confirmation with real-world data matched-pair analysis and further clinical trials to refine and optimize the 177Lu-PSMA therapy administration scheme to improve tumor radiation dose delivery and efficacy.