Abstract 649TiP
Background
After radical prostatectomy, 25% to 35% of patients develop progression of serum prostate-specific antigen (PSA). Positron emission tomography of radiolabelled prostate-specific membrane antigen ligands (PSMA-PET) is more sensitive and specific than conventional imaging for lesion detection. This trial-in-progress (NCT04557059) uses PSMA-PET-evaluated staging and outcomes to investigate adding apalutamide (a next-generation nonsteroidal androgen receptor antagonist) to radiotherapy (RT) and a luteinizing hormone-releasing hormone agonist (LHRHa) in patients with high-risk, PSMA-PET-positive hormone-sensitive prostate cancer, nonmetastatic on conventional imaging.
Trial design
Patients with ≥1 locoregional lesion on PSMA-PET and high-risk biochemical recurrence (either PSA doubling time ≤12 months [mo] or pathologic Gleason score ≥8) after radical prostatectomy are randomised 1:1 to RT + LHRHa or RT + LHRHa + apalutamide. 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. Medications are LHRHa for 6 mo ± apalutamide 240 mg/day for 26 weeks. PSA is measured every 3 mo. PSMA-PET (screening, 6 + 12 mo, then annually or until PSA ≥0.2 ng/mL, then every 6 mo) is assessed by blinded independent central review (BICR). Investigators are blinded to PSMA-PET lesion locations from randomisation until PSMA-PET progression. The primary endpoint is time from randomisation until PSMA-PET distant metastatic progression or death from any cause. Patient-reported outcomes, biomarkers, PSA progression, safety, metastasis by conventional imaging, and survival are assessed. Randomisation of ∼412 patients is ongoing. An exploratory substudy evaluates response with whole-body magnetic resonance imaging. In parallel, PSMA-PET-negative patients at screening enrol in an observational cohort with data collection during routine clinical practice. This is one of the first randomised, controlled trials to use novel imaging for study enrolment and outcomes in prostate cancer with biochemical recurrence.
Clinical trial identification
EudraCT 2019-002957-46; NCT04557059; PRIMORDIUM, 56021927PCR3015.
Editorial acknowledgement
Jonathan Latham, PharmaScribe, LLC, provided editorial assistance.
Legal entity responsible for the study
Janssen Pharmaceutica NV.
Funding
Janssen Pharmaceutica NV.
Disclosure
B.A. Hadaschik: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: ABX; Financial Interests, Personal, Advisory Role: Lightpoint Medical, Inc; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Institutional, Research Grant: German Research Foundation. S. Fanti: Financial Interests, Personal, Advisory Role: AAA; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: GE; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: IBA; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Telix. P. Ost: Financial Interests, Personal, Advisory Role: Ferring; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Varian; Financial Interests, Institutional, Research Grant: Ferring. N. Tunariu: Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Advisory Role: Janssen. C. de Nunzio: Financial Interests, Personal, Advisory Role: Ferring; Financial Interests, Personal, Advisory Role: IBSA; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: PierreFabre; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Omegapharm. L. Antoni: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. M. Lukac: Other, Personal, Project Lead, Contracted: Janssen. J. Martin: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. G. Pissart: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. R. Wapenaar: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. N. Mottet: Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Ferring; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Steba; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Carrik; Financial Interests, Personal, Advisory Role: Arquer Diagnostics; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Sanofi.