Cabozantinib (VEGFR/MET/AXL TKI) + nivolumab (PD-1) doubles PFS in aRCC with baseline bone metastases vs sunitinib

Cabozantinib plus nivolumab (C+N) combines multi-kinase VEGFR/MET/AXL inhibition with PD-1 blockade and was compared with sunitinib in the Phase 3 CheckMate-9ER first-line clear-cell aRCC trial (NCT03141177; N=651); this updated exploratory subgroup analysis focuses on patients with baseline bone metastases (n=154) at ~5-year follow-up (median 67.6 months). In bone-metastatic patients, C+N improved median PFS to 13.8 vs 5.3 months (HR 0.43, 95% CI 0.30–0.64) and median OS to 34.8 vs 20.7 months (HR 0.66, 95% CI 0.45–0.95), with consistent benefit even with additional liver/lung/LN/adrenal disease (e.g., bone+liver mPFS 6.9 vs 3.8 months; bone+lung mPFS 10.0 vs 4.4 months). Versus the historical first-line VEGFR-TKI-only SOC represented here by sunitinib, the efficacy delta looks clinically meaningful in this poor-prognosis subgroup; safety in the bone-metastasis cohort was reported as generally consistent with the overall study population (but subgroup-specific Grade 3+ AE rates were not provided in this abstract).