RT Journal Article SR Electronic T1 177Lu-PSMA-617 versus Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer: a randomised, open-label, phase 2 trial (TheraP) JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1703 OP 1703 VO 62 IS supplement 1 A1 Michael Hofman A1 Louise Emmett A1 Amir Iravani A1 Shahneen Sandhu A1 Anthony Joshua A1 David Pattison A1 Jeffrey Goh A1 Ian Kirkwood A1 Thean Hsiang Tan A1 Roslyn Francis A1 Siobhan Ng A1 Natalie Rutherford A1 Craig Gedye A1 Andrew Scott A1 Sze-Ting Lee A1 Andrew Weickhardt A1 Shakher Ramdave A1 Edmond Kwan A1 Arun Azad A1 William Macdonald A1 Andrew Redfern A1 Alison Zhang A1 Martin Stockler A1 Andrew Martin A1 Ian Davis YR 2021 UL http://jnm.snmjournals.org/content/62/supplement_1/1703.abstract AB 1703Objectives: 177Lu-PSMA-617 is a radiolabelled small molecule that delivers β-radiation to cells expressing prostate specific membrane antigen (PSMA), with promising activity and safety in metastatic castration-resistant prostate cancer (mCRPC). We compared 177Lu-PSMA-617 and cabazitaxel in a randomised phase 2 trial. Methods: Men with mCRPC progressing after docetaxel with high PSMA tumour-expression were randomized to 177Lu-PSMA-617 (6-8.5 GBq intravenously 6 weekly up to 6 cycles) vs cabazitaxel (20 mg/m2 intravenously 3 weekly up to 10 cycles) at 11-sites in Australia. The primary endpoint was prostate specific antigen (PSA) response rate defined by ≥50% reduction (PSA50-RR). Secondary endpoints included progression-free survival (PFS) (PSA and radiographic PFS), objective response rate (ORR) (RECIST 1.1), adverse events (CTCAE v4.03), patient-reported outcomes (PROs) (EORTC QLQ-C30, PDF), and overall survival (OS). This trial is registered in ClinicalTrials.gov, NCT03392428. Results: 200 of 291 men identified as eligible on PET imaging were randomised to 177Lu-PSMA-617 (N=99) or cabazitaxel (N=101). 91% had received prior androgen receptor-directed therapy (ARDT). PSA50-RR was significantly higher in those assigned 177Lu-PSMA-617 versus cabazitaxel (66% [95%CI,56-75%] vs 37% [95%CI,27-46%]; P<0.001). PFS was significantly longer in those assigned 177Lu-PSMA-617 than cabazitaxel (rates at 1yr 19% [95%CI,12-27%] vs 3% [95%CI,1-9%], hazard ratio (HR) 0·63 [95%CI,0.46-0.86; P=0.003). ORR in 78 men with measurable disease was significantly higher with 177Lu-PSMA-617 than cabazitaxel (49% vs 24%, RR 2.12; P=0.026). Follow-up remains immature for OS. Grade 3-4 adverse events occurred in 32/98 (33%) with 177Lu-PSMA-617 vs 45/85 (55%) with cabazitaxel. Overall quality-of-life and health status were similar, with significantly better outcomes for multiple PRO domains including diarrhoea, fatigue, social functioning, insomnia, hair loss, skin rash and sore hands/feet with 177Lu-PSMA-617. Conclusions: 177Lu-PSMA-617 compared to cabazitaxel in men with mCRPC led to significantly higher PSA and ORR response rates, longer PFS, less grade 3 or 4 adverse events and significant improvements in several PRO domains. Acknowledgements: This investigator-initiated trial received support from the Prostate Cancer Foundation of Australia, Endocyte (a Novartis Company), Australian Nuclear Science and Technology Organization (ANSTO), Movember, It’s a Bloke Thing, CAN4CANCER. Results also presented at ASCO GU 2021.