In the phase 2 RADICAL/Alliance A031801 trial (NCT04071223) evaluating cabozantinib (Cabometyx) with or without radium-223 in renal cell carcinoma (RCC) with symptomatic bone metastases, the combination failed to meet its primary end point of symptomatic skeletal event-free survival, leading to early closure due to futility. Despite a numerical trend toward improved overall survival (OS), the regimen also demonstrated a higher rate of grade 3 or greater adverse effects (AEs).
In an interview with CancerNetwork®, María Teresa Bourlon, MD, MSc, FASCO, head of the Urologic Oncology Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, Mexico, advised against over-interpreting secondary survival signals from a trial closed early for futility. She highlighted that added toxicity directly harms patient quality of life without proven clinical benefit. Bourlon emphasized that because the study did not meet its primary end point, the findings remain inconclusive, offering guidance for oncologists navigating treatment selection in bone-metastatic RCC.
Transcript:
CancerNetwork: Adding radium-223 increased grade 3 or higher treatment-related AEs without improving symptomatic skeletal event-free survival. From a multidisciplinary perspective, how should medical and radiation oncologists weigh that added toxicity against the observed survival trend when counseling patients with symptomatic, bone-metastatic RCC?
Bourlon: At this point, we need to understand that this combination won’t get approval. We all understand the rationale for [testing] it, as kidney cancer bone metastases can be very symptomatic, and we’re glad to see a tested drug that could decrease skeletal-related events. Nevertheless, the drug wasn’t able to do this, and the trial closed due to futility.
If we’re seeing higher grade 3 toxicity, that means we’re deteriorating the patient’s quality of life. For a trial that closed early, [the findings] can’t be conclusive about other outcomes such as [OS]. I’d be very cautious about interpreting this combination as improving [OS]. I’d rather view this as a trial with a reasonable hypothesis about a potential synergy between the drugs, designed to decrease skeletal-related events, that closed early due to futility. It’s very hard to interpret any data from this study beyond the fact that it didn’t improve its primary end point.
Reference
McKay RR, Atherton P, Ballman KV, et al. A phase 2 randomized trial of radium-223 dichloride and cabozantinib in patients (pts) with renal cell carcinoma (RCC) with bone metastases (BM): RADICAL (Alliance A031801). J Clin Oncol. 2026;44(suppl 16):4500. doi:10.1200/JCO.2026.44.16_suppl.4500
