Radium Ra-223

Dr. Savita Dandapani presented initial results of the SHARP trial, combining SBRT, hormone/androgen deprivation therapy, and Radium-223 for oligometastatic castrate-sensitive prostate cancer. The trial showed improved PFS and delayed TTF with Radium-223, with better outcomes for patients with de novo oligometastatic disease. Future research includes comparing Radium-223 and Lu177-PSMA in mHSPC and analyzing biomarkers to predict patient benefit.

Dr. Savita Dandapani presented initial results of the SHARP trial at ASTRO 2024, combining SBRT, ADT, and Radium-223 for oligometastatic prostate cancer. The trial showed improved PFS and delayed TTF with Radium-223, with better outcomes for de novo oligometastatic disease. Cytokine analysis indicated potential anti-inflammatory responses, with IL-8 levels rising post-treatment.

Radiopharmaceuticals are crucial in advanced prostate cancer treatment, delivering radiation directly to cancer cells. PSMA imaging enhances detection of disease spread. Radiopharmaceuticals like radium-223 and lutetium-177 are used in metastatic cases post-androgen deprivation therapy. Emerging alpha emitters like actinium-225 show promise. Challenges include earlier disease stage use and widespread access. Combining radiopharmaceuticals with other therapies and improving access are key unmet needs.

Despite numerous treatment options for metastatic castration-resistant prostate cancer (mCRPC), cross-resistance and early-line use of androgen receptor–pathway inhibitors (ARPIs) limit options. Ongoing research focuses on novel agents like AR degraders to address unmet needs. Radioligand therapy and clinical trials are crucial for advancing care, with PSMA imaging and genomic testing reshaping treatment paradigms.

ESMO Congress 2024 featured practice-changing trials in breast, gastrointestinal, genitourinary, and gynecologic cancers, including positive results for hypofractionated nodal radiotherapy in early breast cancer, perioperative pembrolizumab in high-risk TNBC, retifanlimab in advanced squamous cell anal cancer, and pembrolizumab in high-risk cervical cancer, alongside negative findings in CAPItello-290, PANDAS-PRODIGE 44, TiNivo-2, and ATHENA-COMBO trials.

Combining radium-223 with enzalutamide significantly extended radiological progression-free survival and overall survival in advanced prostate cancer patients with bone metastases, according to the PEACE-3 trial. A bone-protecting agent is mandatory when using this combination. The median radiological progression-free survival was 19.4 months in the combination arm vs 16.4 months in the enzalutamide-only arm. Median overall survival was 42.3 months vs 35.0 months, respectively.

Enzalutamide plus radium-223 significantly extends survival in men with castration-resistant prostate cancer and bone metastases, though with increased toxicity.

Radium-223 plus enzalutamide significantly improved radiological progression-free survival (rPFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases, according to PEACE-3 trial data. The combination also extended time to next systemic treatment (TTNT) but did not affect time to pain progression or first symptomatic skeletal event (SSE). Use of a bone-protecting agent was mandatory. Safety data showed higher rates of adverse events in the combination arm, with no drug-related deaths.