ESMO 2021: PRIMORDIUM – A Randomized, International, Trial-in-Progress of Adding Apalutamide to Radiotherapy and an LHRH Agonist in High-Risk Patients With PSMA-PET-Positive Hormone-Sensitive Prostate Cancer

(UroToday.com) In the on-demand poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Boris Hadaschik presented on the trial in progress, PRIMORDIUM (NCT04557059).

This study is designed to assess the role of PSMA-PET-evaluated staging and outcomes in the context of adding apalutamide (a next-generation nonsteroidal androgen receptor antagonist) to radiotherapy (RT) and a luteinizing hormone-releasing hormone agonist (LHRHa) in men with high-risk, PSMA-PET-positive hormone-sensitive prostate cancer who have no evidence of metastatic disease on conventional imaging. This trial is founded on basis of a biochemical recurrence rate of 25 to 35% among men who have previously undergone radical prostatectomy. In the BCR disease state, positron emission tomography of radiolabelled prostate-specific membrane antigen ligands (PSMA-PET) is more sensitive and specific than conventional imaging for lesion detection.

The authors are accruing patients with ≥1 locoregional lesion on PSMA-PET and high-risk biochemical recurrence (defined as either PSA doubling time ≤12 months or pathologic Gleason score ≥8) after radical prostatectomy. After accrual, patients are randomised 1:1 to salvage RT + LHRHa or salvage RT + LHRHa + apalutamide. Salvage RT includes whole pelvic salvage radiotherapy, with stereotactic body radiation therapy for ≤3 PSMA-avid distant metastases at sites where it is a standard approach. In terms of systemic therapy, patients receive LHRHa for 6 months ± apalutamide 240 mg/day for 26 weeks.

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Patients will have PSA measured every 3 months as well as PSMA-PET at screening, 6 months, 12 months, and then annually or until PSA ≥0.2 ng/mL at which time imaging is performed every 6 months). PSMA-PET scans are assessed by blinded independent central review (BICR). The treating investigators are blinded to PSMA-PET lesion locations from randomization until PSMA-PET progression.

The primary study endpoint is the time from randomization until PSMA-PET distant metastatic progression or death from any cause. Additionally, secondary outcomes such as patient-reported outcomes, biomarkers, PSA progression, safety, metastasis by conventional imaging, and survival are assessed.

Currently, randomization of approximately 412 patients is ongoing. In addition to the overall study cohort, an exploratory substudy evaluates response with whole-body magnetic resonance imaging. In parallel, PSMA-PET-negative patients at screening enrolled in an observational cohort with data collection during routine clinical practice.

Presented by: Boris A. Hadaschik, MD, Director and Chair of the Department of Urology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany
Essen, Germany