Results from the Alliance for Clinical Trials in Oncology's Phase II RadiCaL trial (Alliance A031801), the first randomized study of a radiopharmaceutical in kidney cancer, found that adding radium-223 to the standard of care does not improve the length of time patients went without serious bone complications (called skeletal event-free survival) for patients with advanced kidney cancer. The findings are published open access in the Journal of Clinical Oncology .
Each year, 80,000 Americans are diagnosed with kidney cancer. Of those patients, about 30% will have metastatic disease that has spread to other parts of the body. When kidney cancer spreads to the bones, it can cause pain, fractures, and other complications that affect a patient's quality of life and overall survival.
A current treatment for metastatic kidney cancer is cabozantinib, a targeted oral cancer drug that blocks tumor growth and blood supply. Over five years, RadiCaL enrolled 98 patients at 29 cancer centers across the United States to see if adding the radioactive medication radium-223 to cabozantinib would help delay bone complications. Radium-223 mimics calcium, concentrating in bone where it delivers short-range radiation that targets cancer cells while minimizing damage to healthy tissues.
Since both radium-223 and cabozantinib are known to help treat advanced cancer, researchers wanted to see if combining them would offer improve bone protection for patients with bone metastases.
What the RadiCaL Study Found
· Bone Complications Were Less Common Than Expected: Nearly 80% of patients received bone-strengthening medications such as denosumab or bisphosphonates, and skeletal complications occurred far less often than in earlier studies. Adding radium-223 did not further reduce them, suggesting that bone-directed supportive care may already be working well.
· A Survival Finding Worth Further Study: Patients who received the combination treatment lived a median of 28.3 months, compared with 19.7 months for those who received cabozantinib alone. Because the trial was not designed to study overall survival benefit, this difference should be considered hypothesis-generating and warrants further investigation.
· Safe and Feasible: The combination was well tolerated, with similar rates of serious side effects in both groups, establishing that this class of agents can be safely combined with standard kidney cancer therapy.
· Trial Closed After Futility Analysis: The trial closed after the interim analysis showed that adding radium-223 was unlikely to improve the primary endpoint of skeletal event-free survival compared to cabozantinib alone. The findings provide important information to guide future research into approaches for preventing and treating bone complications in patients with advanced kidney cancer.
"RadiCaL is the first randomized trial of a radiopharmaceutical in kidney cancer, and it tells us several important things," said lead author Rana R. McKay, MD, Professor of Medicine at UC San Diego Health and principal investigator for the study. "Skeletal complications were low across the board, which speaks to the effectiveness of modern bone-protective care, that in itself is reassuring news for patients. Radium-223 did not further reduce skeletal complications, but we did see numerically longer survival with the combination of radium-223 and cabozantinib. This finding is hypothesis-generating and needs further investigation. Together with a tolerable side effect profile showing these agents can be safely combined, it tells us that radiopharmaceuticals deserve continued, careful study in kidney cancer."
