Radium Ra-223

Radiotheranostics merges diagnostic and therapeutic capabilities, enhancing precision medicine in oncology through radiopharmaceuticals, with potential applications in cardiology and neurology.

Ursula Vogl discusses key prostate cancer trials from ESMO 2024: PATCH (transdermal estradiol vs. LHRH analogs in non-metastatic), ARANOTE (darolutamide in metastatic hormone-sensitive), and PEACE-3 (radium-223 plus enzalutamide in metastatic castration-resistant). Also covered are STAMPEDE (metformin's metabolic benefits) and SPLASH (lutetium PSMA-I&T therapy). Practical considerations include metformin's potential role despite lacking overall survival benefit and challenges in implementing radioligand therapy due to logistical, regulatory, and reimbursement issues.

PEACE III trial compared enzalutamide with enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer, showing superior efficacy of the triplet over the doublet. Bone-protective agents (BPAs) nearly eliminated fracture risk when used with radium-223. Consider enzalutamide–radium-223 combination in specific patients, and address contraindications and bone support strategies to enhance radium-223 safety.

Prostate cancer stages include localized, locally advanced, non-metastatic castration-resistant (M0 CRPCa), and metastatic disease. Treatments for M0 CRPCa and hormone-naive metastatic prostate cancer include androgen deprivation therapy with apalutamide, darolutamide, or enzalutamide. Metastatic castration-resistant treatments include sipuleucel-T, radium-223, abiraterone, enzalutamide, and cabazitaxel. New drugs like PARP inhibitors and Lutetium-177 aim to improve survival and progression-free survival, with ongoing trials for cabozantinib and chimeric-antigen receptor T-cell therapy.

Øyvind Bruland discusses his journey from traditional oncology to radiopharmaceuticals, focusing on alpha particles for treating chemotherapy-resistant disease. He highlights Oncoinvent's work with radium-224 microparticles for peritoneal carcinomatosis, showing early success in colorectal and ovarian cancer patients. The conversation explores future combination therapies, including alpha-beta combinations and immunotherapy partnerships, emphasizing the importance of dosing, timing, and understanding stromal manipulation for treatment efficacy.

PEACE-3 trial data suggests radium-223 plus enzalutamide could be a new first-line treatment for metastatic castration-resistant prostate cancer, with significant improvements in radiographic progression–free survival and overall survival.

The RAVENS study found no delay in disease progression with the addition of radium-223 (Ra223) to stereotactic ablative radiotherapy (SABR) for bone-metastatic oligometastatic hormone-sensitive prostate cancer, contrary to the hypothesis. Median progression-free survival (PFS) was 11.8 months in the SABR arm vs 10.5 months in the SABR/Ra223 arm. Ra223's mechanism of action may be less effective when bone lesions are eradicated by SABR, suggesting potential benefits in higher volume disease.

RAVENS phase 2 trial results show no benefit of adding radium-223 to stereotactic ablative radiotherapy for oligometastatic prostate cancer, with similar progression-free survival rates. The study highlights the need for biomarker research in this field.

The FDA's approval of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in 2022 has significantly impacted the treatment of prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC). This radioligand therapy, after other treatments like ARPIs and taxane-based chemotherapy, has shown life-prolonging effects and improved quality of life. Potential future applications include earlier use in the treatment paradigm and combination therapies, with ongoing research aiming to establish a broader role for this treatment type.