Cabozantinib (VEGFR/MET/AXL TKI) + nivolumab (PD-1) sustains PFS/OS gains vs sunitinib in aRCC with liver metastases

Cabozantinib is a multikinase VEGFR/MET/AXL inhibitor paired here with nivolumab, a PD-1 checkpoint inhibitor; this exploratory CheckMate-9ER (Phase 3; NCT03141177) subgroup analysis evaluated first-line clear-cell aRCC with baseline liver metastases (LM; n=129) versus no LM (NLM), with median follow-up 67.6 months. In LM+any-site patients, C+N improved mPFS to 10.9 vs 6.2 months (HR 0.55, 95% CI 0.37–0.82) and mOS to 37.6 vs 22.1 months (HR 0.65, 95% CI 0.43–0.97) versus sunitinib; NLM patients similarly favored C+N (mPFS 18.4 vs 9.2 months; HR 0.59, 95% CI 0.48–0.71; mOS 49.5 vs 39.7 months). Outcomes were poorest with LM+bone metastases (mPFS 6.9 vs 3.8 months; HR 0.77, wide CI), but relative benefit remained directionally consistent across LM subgroups; safety in LM appeared consistent with the overall population, and LM did not reduce cabozantinib exposure (median daily dose 31.8 mg in LM vs 26.3 mg in NLM). Versus historical sunitinib benchmarks in front-line mRCC (mPFS often ~10–11 months in intermediate/poor-risk populations), the sunitinib LM subgroup here looks particularly high-risk (mPFS 6.2 months), and C+N brings it back into a more “typical” range while also extending OS by ~15.5 months.