Cabozantinib plus nivolumab (C+N) versus sunitinib (S) in patients with advanced renal cell carcinoma (aRCC) and liver metastasis: Subgroup analysis of the phase 3 CheckMate-9ER trial.

Abstract

4530 Background: In the phase 3 CheckMate 9ER trial (NCT03141177), C+N treatment significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in patients with first-line aRCC, including those with baseline LM (Motzer et al. Ann Oncol 2026). We performed exploratory analyses of outcomes in additional subgroups including patients with no LM (NLM) and those with LM plus other metastatic sites. Methods: 651 patients with clear-cell aRCC were randomized 1:1 to C (40 mg QD) + N (240 mg Q2W) or S (50 mg QD for 4 weeks of 6-week cycles). PFS (primary endpoint) and ORR were per RECIST v1.1 by blinded independent central review. Median f-u was 67.6 mo. Patient subgroups analyzed included those with LM or NLM at baseline and those with bone, lung, lymph node (LN), or adrenal gland metastasis in addition to LM. Results: 129 patients had LM at baseline. Baseline characteristics were generally consistent between treatment arms among patients with LM and NLM. A PFS and OS benefit with C+N vs S was observed in patients with LM and NLM (Table). Both subgroups experienced greater ORR and longer duration of response (DOR) with C+N vs S. Although outcomes were less favorable in those with vs without LM, and least favorable in those with both LM and bone metastasis, the relative benefit with C+N vs S was consistent across metastatic site subgroups. The safety profile among patients with LM was generally consistent with the overall population. Presence of LM did not negatively impact C dose exposure (median daily dose 31.8 mg in LM; 26.3 mg in NLM). Conclusions: Treatment with C+N vs S improved efficacy outcomes in patients with first-line aRCC irrespective of LM at baseline. Among patients with LM, a consistent benefit was observed regardless of concomitant metastasis in bone, lung, LN, or adrenal gland. Clinical trial information: NCT03141177 . Efficacy by metastatic sites. Subgroup(C+N v S) LM + Any Site(s) a (n=73 v n=56) NLM(n=250 v n=272) LM + Bone(n=15 v n=17) LM + Lung(n=46 v n=43) LM + LN(n=31 v n=27) LM + Adrenal Gland(n=8 v n=6) mPFS, mo 10.9 v 6.2 b 18.4 v 9.2 6.9 v 3.8 9.1 v 4.1 9.7 v 6.2 32.0 v 2.0 PFS HR (95% CI) 0.55 (0.37, 0.82) b 0.59 (0.48, 0.71) 0.77 (0.33, 1.76) 0.50 (0.32, 0.80) 0.65 (0.36, 1.17) 0.18 (0.04, 0.78) mOS, mo 37.6 v 22.1 b 49.5 v 39.7 20.9 v 12.7 40.1 v 13.4 34.8 v 13.4 46.3 v 2.0 OS HR (95% CI) 0.65 (0.43, 0.97) b 0.83 (0.66, 1.03) 0.57 (0.26, 1.24) 0.49 (0.30, 0.79) 0.59 (0.33, 1.05) 0.10 (0.02, 0.53) ORR, % 52 v 21 b 57 v 29 40 v 18 52 v 23 48 v 19 88 v 17 mTTR, mo 2.8 v 4.0 2.8 v 5.4 2.9 v 3.0 2.8 v 3.5 2.8 v 4.1 2.8 v 11.1 mDOR, mo 20.7 v 17.8 22.1 v 15.2 12.6 v 6.4 23.1 v 15.8 33.0 v 17.9 41.5 v NR a Only 7 patients had liver-only disease (n=2, C+N; n=5, S), precluding meaningful analysis of this subgroup. b Motzer et al. Ann Oncol 2026. m, median; NR, not reached; TTR, time to response.