Lutetium-177-PSMA-I&T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial

• Published in: BMC cancer Vol. 20; no. 1; p. 884
• Main Authors: Privé, Bastiaan M, Janssen, Marcel J R, van Oort, Inge M, Muselaers, Constantijn H J, Jonker, Marianne A, de Groot, Michel, Mehra, Niven, Verzijlbergen, J Fred, Scheenen, Tom W J, Zámecnik, Patrik, Barentsz, Jelle O, Gotthardt, Martin, Noordzij, Walter, Vogel, Wouter V, Bergman, Andries M, van der Poel, Henk G, Vis, André N, Oprea-Lager, Daniela E, Gerritsen, Winald R, Witjes, J Alfred, Nagarajah, James
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.09.2020; BioMed Central
• Subjects: Androgen Antagonists - administration & dosage; Androgen Antagonists - adverse effects; Antigens; Cancer metastasis; Cancer therapies; Care and treatment; Castration; Clinical trials; Disease Progression; Dosimetry; Health aspects; Hormones; Hormones - genetics; Hormones - metabolism; Humans; Ligands; Lutetium - administration & dosage; Lutetium - adverse effects; Magnetic resonance imaging; Male; Medical prognosis; Medical research; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - radiotherapy; Pain; Patients; Pets; Progression-Free Survival; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - pathology; Prostatic Neoplasms, Castration-Resistant - radiotherapy; Quality of Life; Radiation therapy; Radioisotopes; Radioisotopes - administration & dosage; Radioisotopes - adverse effects; Radiopharmaceuticals - administration & dosage; Rare earth metal compounds; Study Protocol; Surgery; Toxicity; Treatment Outcome; Tumors; Xerostomia; Netherlands; Radioligand therapy; Lutetium-177-PSMA; Hormone sensitive prostate Cancer; Oligometastases; Urologic oncology; Metastases directed therapy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-07386-z

In recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using Lu-PSMA-I&T in a randomized multicenter setting. This study compares Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression. This is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of Lu-PSMA-I&T for patients with oHSPC. Clinicaltrials.gov identifier: NCT04443062 .