Radioligand Therapy for Metastatic Prostate Cancer.

Abstract

HomeRadiology: Imaging CancerVol. 3, No. 6 Previous Research HighlightsFree AccessRadioligand Therapy for Metastatic Prostate CancerBrian J. BurkettBrian J. BurkettBrian J. BurkettPublished Online:Nov 26 2021https://doi.org/10.1148/rycan.2021219026MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: Efficacy of lutetium-177 (177Lu)–prostate-specific membrane antigen (PSMA)–617 radioligand therapy with standard-of-care therapy compared to standard of care alone for castration-resistant metastatic prostate cancer.■ Key Result: 177Lu-PSMA-617, in addition to standard of care, prolongs progression-free survival and overall survival in patients with castration-resistant metastatic prostate cancer selected on the basis of PSMA-ligand PET/CT findings.■ Impact: The phase III VISION trial is the basis for U.S. Food and Drug Administration priority review of 177Lu-PSMA-617 as a new radioligand therapy for appropriately selected patients with pretreated, metastatic prostate cancer. Theranostic agent 177Lu-PSMA-617 is composed of 177Lu (a therapeutic beta-particle emitter) paired with PSMA, a cell surface glycoprotein expressed in most prostate cancer metastases. The pairing allows selective delivery of targeted radiation therapy to prostate cancer cells.The VISION trial is a phase III prospective clinical trial investigating 177Lu-PSMA-617 in the context of previously treated metastatic prostate cancer in combination with several standard-of-care options, including antiandrogen chemotherapeutic agents, external beam radiation therapy, bisphosphonates and denosumab, and steroids. Eligible patients must have progressed while receiving androgen receptor inhibitor and taxane-based chemotherapy and have undergone gallium-68–PSMA-11 PET/CT demonstrating one or more metastatic lesions with tracer uptake. Patients with PSMA-negative metastases 1 cm or larger were ineligible.Five hundred eighty-one patients were randomized to four to six cycles of 177Lu-PSMA-617 with trial-approved standard of care or only standard of care in a 2:1 ratio. 177Lu-PSMA-617 treatment significantly prolonged progression-free survival on the basis of imaging (8.7 vs 3.4 months, hazard ratio of 0.4 [95% CI: 0.29, 0.57]) and significantly prolonged median overall survival (15.3 vs 11.3 months, hazard ratio of 0.62 [95% CI: 0.52, 0.74]). 177Lu-PSMA-617 also significantly prolonged time to first symptomatic skeletal event or death, decreased prostate-specific antigen levels, and increased percentage of tumor response (complete and partial). Adverse events, most commonly fatigue, nausea, or dry mouth, happened more frequently in the group receiving 177Lu-PSMA-617. Five fatal events occurred in the 177Lu-PSMA-617 group due to pancytopenia, bone marrow failure, and intracranial bleeding.This trial complements the phase II TheraP trial that compared 177Lu-PSMA-617 alone to cabazitaxel chemotherapy. The survival benefit reported in the VISION trial ultimately may result in regulatory approval of 177Lu-PSMA-617 administered with other therapeutic options, even in heavily pretreated patients with refractory metastatic disease. PSMA-ligand PET also provides a companion diagnostic imaging marker for selecting appropriate patients and monitoring response to therapy if 177Lu-PSMA-617 receives regulatory approval.Highlighted ArticleSartor O, de Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 2021;385(12):1091– 1103. doi: https://doi.org/10.1056/nejmoa2107322Highlighted ArticleSartor O, de Bono J, Chi KN, et al. Lutetium-177EN_DASHPSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 2021;385(12):1091–1103. doi: https://doi.org/10.1056/nejmoa2107322 Crossref, Medline, Google ScholarArticle HistoryPublished online: Nov 26 2021 FiguresReferencesRelatedDetailsRecommended Articles 177Lu–Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate CancerRadiology2022Volume: 306Issue: 2Prostate-specific Membrane Antigen PET in Prostate CancerRadiology2021Volume: 299Issue: 2pp. 248-260Revisiting Prostate Cancer Recurrence with PSMA PET: Atlas of Typical and Atypical Patterns of SpreadRadioGraphics2019Volume: 39Issue: 1pp. 186-212Radiotheranostics in Cancer Diagnosis and ManagementRadiology2018Volume: 286Issue: 2pp. 388-400Impact of 18F-DCFPyL PET on Staging and Treatment of Unfavorable Intermediate or High-Risk Prostate CancerRadiology2022Volume: 304Issue: 3pp. 600-608See More RSNA Education Exhibits Current Status and Future Prospects in Radioligand TherapyDigital Posters2020Peptide Receptor Radionuclide Therapy (PRRT): 2019 UpdateDigital Posters2019Advanced Prostate Cancer: Update on Evolving Concepts, Rationale, and Challenges of Imaging and Novel Therapeutic StrategiesDigital Posters2018 RSNA Case Collection Radioembolization of Liver Metastasis RSNA Case Collection2020Locally advanced, metastatic prostate adenocarcinomaRSNA Case Collection2020Parasagittal meningiomaRSNA Case Collection2022 Vol. 3, No. 6 Metrics Altmetric Score PDF download