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

Abstract

4528 Background: In first-line aRCC, C+N significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in the phase 3 CheckMate 9ER trial (NCT03141177; Motzer et al. Ann Oncol 2026). In an exploratory analysis with median 18.1-mo f-u, C+N improved PFS, OS, and ORR vs S in patients with or without bone metastasis at baseline. We performed an updated exploratory analysis of outcomes by baseline bone metastasis status based on the 5-year update and analyzed subgroups with additional 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). Median f-u was 67.6 mo. PFS (primary endpoint) and ORR were per RECIST v1.1 by blinded independent central review. Patient subgroups analyzed here include those with or without bone metastasis at baseline and those with liver, lung, lymph node (LN), or adrenal gland metastasis in addition to bone metastasis. Results: 154 patients had bone metastasis at baseline. Baseline characteristics were generally consistent between treatment arms for subgroups with and without bone metastasis. PFS and OS were prolonged with C+N vs S in patients with or without bone metastasis (Table). The ORR was higher and duration of response (DOR) was longer with C+N vs S in both groups. Although outcomes were less favorable in those with vs without bone metastasis, the relative benefit with C+N vs S was consistent across metastatic site subgroups. The safety profile among patients with bone metastasis was generally consistent with the overall population. Conclusions: With additional follow-up, a consistent benefit was maintained for C+N vs S in patients with or without bone metastasis. Among patients with bone metastasis, a consistent benefit was observed regardless of concomitant metastasis in liver, lung, LN, or adrenal gland. Clinical trial information: NCT03141177 . Efficacy by metastatic sites. Subgroup(C+N v S) Bone + Any Site(s) a (n=79 v n=75) No Bone(n=244 v n=253) Bone + Liver(n=15 v n=17) Bone + Lung(n=57 v n=58) Bone + LN(n=33 v n=38) Bone + Adrenal Gland(n=10 v n=8) mPFS, mo 13.8 v 5.3 b 16.6 v 9.5 6.9 v 3.8 10.0 v 4.4 9.0 v 4.1 15.2 v 5.7 PFS HR (95% CI) 0.43 (0.30, 0.64) b 0.60 (0.49, 0.74) 0.77 (0.33, 1.76) 0.45 (0.29, 0.70) 0.50 (0.29, 0.87) 0.62 (0.19, 2.07) mOS, mo 34.8 v 20.7 b 49.5 v 41.0 20.9 v 12.7 31.6 v 22.1 21.3 v 17.5 54.4 v 31.0 OS HR (95% CI) 0.66 (0.45, 0.95) b 0.85 (0.68, 1.06) 0.57 (0.26, 1.24) 0.72 (0.47, 1.10) 0.72 (0.43, 1.20) 0.72 (0.21, 2.50) ORR, % 49 v 9 b 58 v 33 40 v 18 51 v 10 42 v 5 70 v 13 mTTR, mo 2.9 v 7.3 2.8 v 4.3 2.9 v 3.0 2.8 v 5.7 2.9 v 3.4 4.0 v 11.0 mDOR, mo 18.0 v 6.9 22.9 v 15.4 12.6 v 6.4 18.0 v 6.7 16.7 v NC 14.4 v 19.3 a Only 9 patients had bone-only disease (n=7, C+N; n=2, S), precluding meaningful analysis of this subgroup. b Motzer et al. Ann Oncol 2026. m, median; NC, not calculable; TTR, time to response.