ASCO GU 2023: Initial Results of a Phase 2 Pilot Study of Radium-223 and Radiotherapy in Untreated Hormone-Naïve Men with Oligometastatic Prostate Cancer to Bone

( On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on prostate cancer, Dr. Jonathan Tward presented in Poster Session A on a novel approach to treatment of patients with hormone-naïve, oligometastatic prostate cancer to bone with a combination of radium-223 and radiotherapy.

The ALSYMPCA trial demonstrated the overall survival benefit of Radium-223 (Ra223) in men with metastatic castration resistant prostate cancer. However, it has not been used in earlier disease settings. Recently, SBRT metastasis-directed therapy has been shown to delay the time of initiation of systemic therapy in men with oligometastatic prostate cancer. In this study, the authors sought to assess whether the combination of Ra223 with radiation to ≤5 sites of bony metastases could safely delay the time to start androgen deprivation therapy (ADT) and maintain quality of life (QoL).

To assess this hypothesis, the authors enrolled 20 men previously treated with surgery, radiation, or both for M0 PCa who later developed metastatic disease with 5 or fewer bone-only metastatic sites (NCT03304418). Patients further had to have testosterone ≥ 100 ng/dL and evidence of metastatic disease on conventional bone scan, validated by a CT, MRI, or PET/CT. Patients were excluded if they had received LHRH therapies after initial treatment, or had evidence of N1 disease at diagnosis of bone metastasis. Patients were treated with 6 cycles of Ra223 and SBRT (30 Gy in 5 fractions between cycles 1-2). Bone scan was performed at baseline and every 3 months. Additionally, PSA was evaluated monthly during the Ra223 course and every 3 months after. Therapeutic effectiveness was defined as ≥20% of patients meeting the primary endpoint of freedom from ADT (FFAdt) use at 15 months.

Patients stopped study therapy if they had a PSA rise > 10% if their baseline PSA was >20ng/ml or an increase in PSA to greater than 20 if baseline PSA <20 ng/ml. Patients would additionally stop study therapy if they had evidence of disease progression based on a radiographic progression or a skeletal-related event (SRE). All endpoints were timed from the Cycle 1 radium date and patients were followed for 2 years.

Clinically significant changes in patient-reported outcome (PRO) measures were defined as more than one-half standard deviation from the mean baseline value and were censored after the time of ADT use. Continuous and categorical covariates were compared using the Wilcoxon rank sum and Pearson’s Chi2 tests, respectively, and univariate Cox regression. Statistical significance was considered at P<0.05.

Among the 20 enrolled men, the median number of Ra223 cycles was 6 with 6 patients receiving fewer than 6 cycles (range 2-5) due to progression. FFAdt at 15 and 24 Months were 49.5% and 38.5%, respectively (p<0.001). The median time to the initiation of ADT was 14.8 months.

There were no significant changes from baseline in any patient-reported QoL domain (physical functioning, anxiety, depression, fatigue, satisfaction with participation in social roles, sleep disturbance, and pain interference). There were 2 patients with Grade 3 SREs (bone fracture, pain). Grade 2 or greater events attributed as possible or likely due to Ra-223 were seen in 4 patients: bone pain, fatigue, fracture, decreased WBC count, and other. Additionally, two patients had Grade 2 or greater events attributed as possible or likely to EBRT: fatigue and other pain.

The authors, therefore, concluded that first-line use of Ra223 and SBRT to oligometastatic disease sites in hormone-naïve men in this prospective pilot study resulted in a significant delay in ADT use compared to historical control, is well tolerated, and maintains QoL.

Presented by: Jonathan David Tward, MD, PhD | Hunstman Cancer Institute at the University of Utah