TAT-11: A Radiation Oncologist Perspective
In this trial, patients had 2 or more bone metastases and no visceral metastases. All patients had been previously treated or were unfit) with the chemo agent docetaxel and received the best standard of care. The primary endpoint was overall survival, and secondary endpoints were the time to the first symptomatic skeletal event (SSE, such as a fracture or spinal cord compression) and reduced alkaline phosphatase (ALP) levels.
The study showed a significant increase in median overall survival of 14.9 months with Ra223 compared with 11.3 for placebo. This trend was observed over all subgroups. The median time to first SSE was also improved as was the time to first opioid use. Patient-reported quality-of-life also favored the radium treatment. The dramatic results of ALSYMPCA led to FDA approval of Xofigo® (Radium - 223) as the first approved target alpha therapy.
Dr. Morgan described a case study at Ottawa Hospital where a patient had a radical prostatectomy in 1989. In 1994, the patient has a PSA of 2.3, rising to 4.1 in 1998. A bone scan was negative. By the time the patient started on Radium - 223 (an ALSYMPCA participant) the PSA had risen to 16. Over the course of the radium treatment the bone scan improved, there was not much response in PSA but there was a dramatic decrease in ALP. Population studies confirmed the improvement in ALP. Dr. Morgan noted that ALP is correlated with OS, but is not a surrogate. If a patient exhibits an increased ALP, he recommended considering imaging to monitor progression.
As a cautionary tale, Dr. Morgan described the ERA223 trials which paired abiraterone, a second-generation hormone therapy that inhibits CYP17 enzyme for androgen biosynthesis, with Radium - 223 treatment. The trial was stopped after the increased incidence of bone fractures and deaths in the Abi-Radium-223 arm compared to abiraterone alone. It is not clear why the trial failed but one possibility is that lower tumor burden may encourage radium uptake in healthy bone tissue since it was noted that 79% of fractures in the Radium-223 arm occurred at sites without bone metastases.
Presented by: Scott Morgan, MD, Radiation Oncologist, The Ottawa Hospital and Assistant Professor of Radiation Oncology, University of Ottawa
Written by: William Carithers, Lawrence Berkeley National Laboratory at the 11th International Symposium on Targeted Alpha Therapy (TAT-10) April 1 - April 4, 2019 - Ottawa, ON, Canada