Radionuclide therapy directed towards prostate-specific membrane antigen (PSMA) demonstrated promising results in men with docetaxel-treated metastatic castration-resistant prostate cancer (mCRPC) [1]. A phase 2 trial compared radionuclide therapy using lutetium-177 (Lu177) with chemotherapy using cabazitaxel and found greater reductions in prostate-specific antigen (PSA) levels, longer periods of progression-free survival (PFS), and greater objective tumor response rates (ORR). The TheraP trial (NCT03392428) randomized 200 men with docetaxel-treated mCRPC to receive either ≤6 cycles of radionuclide therapy with Lu177 or ≤10 cycles of chemotherapy with cabazitaxel. The primary outcome measure was PSA response rate, defined as the proportion of participants in each group with a ≥50% reduction in PSA from baseline. In the Lu177 group, 65 men (66%) achieved this outcome, as compared with 37 men (37%) in the cabazitaxel group. Key secondary endpoints included PFS, ORR, overall survival (OS), pain intensity, frequency and severity of adverse events, and patient-reported outcomes (PROs). PFS encompassed 3 domains: PSA progression, pain progression, and radiographic progression. After a median follow-up period of 18.4 months, PFS was 19% in the radiotherapy group versus only 3% in the cabazitaxel group. ORR was 49% in the Lu177 group and 24% in the chemotherapy group. OS will be monitored for 4 years; researchers do not yet have data since the study reached its completion date January 2021. To date, 90 deaths are reported. Pain was reported by 60% of participants in the radiotherapy arm and 43% of participants in the cabazitaxel arm. Fewer grade 3 and 4 adverse events occurred in the Lu177 group compared with the cabazitaxel group (33% vs 53%). Investigators utilized the European Organization for Research and Treatment for Cancer (EORTC) core quality of life questionnaire (QLQ-C30) and the Patient Disease and Treatment Assessment Form instruments to capture PROs. The radionuclide group reported superior outcomes in the fatigue, social functioning, insomnia, and diarrhea domains. No domains were superior in the chemotherapy group.
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  1. Hofman M. 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: Updated results including progression-free survival (PFS) and patient-reported outcomes (PROs) (TheraP ANZUP 1603). ASCO Genitourinary Cancers Symposium, 11–13 February 2021.