New data from the phase 2 SHARP trial suggests that a combination therapy involving radium-223 dichloride (Ra-223), stereotactic body radiation therapy (SBRT), and 36 weeks of androgen deprivation therapy (ADT) is both well-tolerated and efficacious for improving overall and progression-free survival (PFS) in patients with metastatic castrate-sensitive prostate cancer (mCSPC).
The findings, presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting, highlight the potential of this combination therapy, particularly in treating oligometastatic cases of CSPC, and have led to a phase 3 trial and long-term follow-up analysis.
SHARP Trial Details
The SHARP trial aimed to combine radiopharmaceuticals and SBRT, an approach that had not been previously explored. Savita Dandapani, MD, PhD, from City of Hope, noted that previous trials have shown the benefit of adding metastasis-directed therapy to oligometastatic sites.
Building on the phase 3 ALSYMPCA trial, which demonstrated an overall survival benefit in castrate-resistant prostate cancer patients treated with Ra-223, Dandapani and her team investigated whether earlier application of radiotherapy in hormone-sensitive prostate cancer could treat micro-metastases, with SBRT serving as a backbone therapy alongside ADT.
While the statistical significance of the primary outcome is still being determined, the trial observed a median PFS of greater than 21 months in treated patients. Dandapani noted that other trials using SBRT alone typically reported PFS of about a year to a year and a half. The benefit was even more pronounced in patients with de novo oligometastic disease, with PFS exceeding 30 months.
MRI-Guided SBRT Reduces Toxicity
In a separate study, the MIRAGE trial, MRI-guided SBRT was compared to CT-guided SBRT for prostate cancer. The results showed that aggressive margin reduction using MRI guidance reduced acute grade 2+ genitourinary and gastrointestinal toxicity following prostate SBRT. Patients treated with MRI guidance had significantly lower rates of 2x minimal clinically important difference in the urinary irritative (19.2% vs. 35.3%, p = 0.03) and bowel (26% vs. 4%, p = 0.04) domains.
RAVENS Trial: Radium-223 and SABR
The RAVENS phase 2 randomized trial assessed outcomes of radium-223 + stereotactic ablative radiotherapy (SABR) versus SABR alone for oligometastatic prostate cancer. The study found that the addition of radium-223 to SABR metastasis-directed therapy in low-volume bone-metastatic hormone-sensitive prostate cancer did not delay progression of disease. Median PFS was 11.8 months in the SABR arm vs 10.5 months in the SABR/Ra223 arm (HR, 1.37; 95% CI: 0.78-2.39, P = .27).
PACE-B Trial: SBRT Noninferior to Conventional Radiotherapy
Data from the phase 3 PACE-B trial, published in the New England Journal of Medicine, showed that five-fraction stereotactic body radiotherapy (SBRT) demonstrated a comparable rate of biochemical and clinical failure vs conventionally or moderately hypofractionated radiotherapy regimens in patients with localized prostate cancer. Specifically, 95.8% of patients in the SBRT arm were free from biochemical or clinical failure at 5 years compared with 94.6% of patients in the control radiotherapy arm (HR, 0.73; 95% CI, 0.48-1.12; P = .004 for noninferiority).
