Radium-223 (bone-seeking alpha emitter) + cabozantinib (VEGFR/MET/AXL TKI) misses SSE-free survival in RCC bone metastases

Radium-223 dichloride is a bone-targeted alpha-emitting radiopharmaceutical, and cabozantinib is a multikinase VEGFR/MET/AXL inhibitor with known activity in RCC bone disease; RADICAL (Alliance A031801; NCT04071223) randomized pts with RCC and ≥1 symptomatic, non-irradiated bone metastasis to cabozantinib + radium-223 (Arm A) vs cabozantinib alone (Arm B) in a Phase 2 open-label multicenter design (n=90; 83.3% clear cell; 88.9% previously treated; 80.0% on osteoclast-targeted therapy). At interim (median follow-up 13.1 mo; 50 events), the primary endpoint was negative and triggered futility: stratified median SSE-free survival 17.9 vs 17.6 mo (HR 1.24), with similar ORR in evaluable pts (22.2% vs 22.9%; 71 evaluable) and similar PFS (11.0 vs 11.2 mo; HR 1.39); OS numerically favored the combination (32.2 vs 21.3 mo; HR 0.77) but with wide CIs and limited events. Toxicity was high in both arms—as expected for cabozantinib in a symptomatic BM population—with grade ≥3 TRAEs 65.9% vs 56.8% (any-grade 97.7% vs 93.2%); efficacy looks broadly in the ballpark of historical post-VEGFR-TKI cabozantinib benchmarks (METEOR: ORR ~17%, mPFS ~7.4 mo, mOS ~21.4 mo vs everolimus), noting RADICAL’s bone-met–enriched, SSE-focused population and frequent concurrent bone agents.