Cabozantinib (VEGFR/MET/AXL TKI) + Radium-223 (bone-seeking α-emitter) fails to extend SSE-free survival in mRCC bone mets (RADICAL)

Radium-223 dichloride is an osteotropic alpha-particle radiopharmaceutical, combined here with cabozantinib, an oral multikinase TKI (VEGFR2/MET/AXL) with known activity in RCC bone disease; RADICAL (Alliance A031801; NCT04071223) randomized Phase II cabozantinib ± radium-223 in mRCC (any histology) with ≥1 bone metastasis (n=98; 82.7% clear cell; 79.6% on osteoclast-targeted therapy; median follow-up 13.1 months) and stopped early for futility at interim. Median SSE-free survival was 16.7 vs 17.6 months (stratified HR 1.46; 90% CI 0.86–2.51), ORR 19.4% vs 25.0% (P=.78), and median OS 28.3 vs 19.7 months (sHR 1.40; 95% CI 0.70–2.79), with similar grade ≥3 AEs (69.6% vs 75.5%); the efficacy readout broadly sits within what you’d expect for cabozantinib alone in previously treated mRCC (e.g., METEOR reported ORR ~17% and median OS ~21.4 months vs everolimus), but importantly shows no skeletal-event signal when adding radium-223.