RT Journal Article SR Electronic T1 Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 857 OP 865 DO 10.2967/jnumed.119.236414 VO 61 IS 6 A1 John Violet A1 Shahneen Sandhu A1 Amir Iravani A1 Justin Ferdinandus A1 Sue-Ping Thang A1 Grace Kong A1 Aravind Ravi Kumar A1 Tim Akhurst A1 David Pattison A1 Alexis Beaulieu A1 Jennifer Mooi A1 Ben Tran A1 Christina Guo A1 Victor Kalff A1 Declan G Murphy A1 Price Jackson A1 Peter Eu A1 Mark Scalzo A1 Scott Williams A1 Rodney J. Hicks A1 Michael S. Hofman YR 2020 UL http://jnm.snmjournals.org/content/61/6/857.abstract AB 177Lu-PSMA-617 is a radioligand with high affinity for prostate-specific membrane antigen (PSMA), enabling targeted β-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castration-resistant prostate cancer. We now report their longer-term outcomes, including a 20-patient extension cohort and outcomes of subsequent systemic treatments after completion of trial therapy. Methods: Fifty patients with PSMA-avid metastatic castration-resistant prostate cancer who had progressed after standard therapies received up to 4 cycles of 177Lu-PSMA every 6 wk. Endpoints included prostate-specific antigen (PSA) response (Prostate Cancer Working Group 2), toxicity (Common Terminology Criteria for Adverse Events, version 4.03), imaging response, patient-reported health-related quality of life, progression-free survival, and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including 177Lu-PSMA. Results: Seventy-five men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 mo) and extensive prior treatment, including prior docetaxel (84%), cabazitaxel (48%), and abiraterone or enzalutamide (92%). The mean administered radioactivity was 7.5 GBq/cycle. A PSA decline of at least 50% was achieved in 32 of 50 patients (64%; 95% confidence interval [CI], 50%–77%), including 22 patients (44%; 95% CI, 30%–59%) with at least an 80% decrease. Of 27 patients with measurable soft-tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to 177Lu-PSMA were self-limiting G1–G2 dry mouth (66%), transient G1–G2 nausea (48%), G3–G4 thrombocytopenia (10%), and G3 anemia (10%). Brief Pain Inventory severity and interference scores decreased at all time points, including at the 3-mo follow-up, with a decrease of −1.2 (95% CI, −0.5 to −1.9; P = 0.001) and −1.0 (95% CI, −0.2 to −0.18; P = 0.013), respectively. At a median follow-up of 31.4 mo, median overall survival was 13.3 mo (95% CI, 10.5–18.7 mo), with a significantly longer survival of 18.4 mo (95% CI, 13.8–23.8 mo) in patients achieving a PSA decline of at least 50%. At progression after prior response, further 177Lu-PSMA was administered to 15 (30%) patients (median of 2 cycles commencing 359 d from enrollment), with a PSA decline of at least 50% in 11 patients (73%). Four of 21 patients (19%) receiving other systemic therapies on progression experienced a PSA decline of at least 50%. There were no unexpected adverse events with 177Lu-PSMA retreatment. Conclusion: This expanded 50-patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity, and improved quality of life with 177Lu-PSMA radioligand therapy. On progression, rechallenge 177Lu-PSMA demonstrated higher response rates than other systemic therapies.