Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial.
Authors: Robert J. Motzer, Bernard Escudier, Mauricio Burotto, Thomas Powles, Andrea B Apolo, Maria T. Bourlon, Amishi Yogesh Shah, Camillo Porta, Cristina Suárez, Carlos H. Barrios, Martin Eduardo Richardet, Howard Gurney, Elizabeth R. Kessler, Yoshihiko Tomita, Jens Bedke, Fatima A. Rangwala, Margarita Askelson, Julie Panzica, Viktor Fedorov, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2025)

439 Background: N+C showed significant benefits vs S in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for patients (pts) with previously untreated aRCC from the phase 3 CheckMate 9ER trial ( N Engl J Med 2021; 384:829–41). We report final results for the trial with a long-term follow-up (min, &gt;5 y), including updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety. Methods: Pts with aRCC were randomized to receive first-line N 240 mg every 2 wk + C 40 mg QD or S 50 mg QD (4 wk of each 6-wk cycle) until disease progression or unacceptable toxicity (2 y N max.). The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Median follow-up was 67.6 (range, 60.2–80.2) mo. In ITT pts (N+C, n = 323; S, n = 328), PFS favored N+C vs S (hazard ratio [HR], 0.58 [95% CI, 0.49–0.70]). Median (95% CI) PFS (mPFS) was 16.4 (12.5–19.3) vs 8.3 (7.0–9.7) mo, respectively; 60-mo PFS rates were 13.6% vs 3.6%. OS also favored N+C vs S (HR, 0.79 [95% CI, 0.65–0.96]). Median (95% CI) OS (mOS) was 46.5 (40.6–53.8) vs 35.5 (29.2–42.8) mo, respectively; 60-mo OS rates were 40.9% vs 35.4%. ORR was greater with N+C vs S (55.7% vs 27.4%; complete response [CR], 13.9% vs 4.6%). Duration of response (DOR) rates at 60 mo with N+C vs S were 22.0% vs 10.0%, respectively. Efficacy by IMDC risk groups is reported in the Table. In all treated pts (n = 320 each arm), any-grade (grade ≥ 3) treatment-related adverse events occurred in 97.5% (67.8%) vs 93.1% (55.3%) with N+C vs S. No new deaths due to study drug toxicity occurred since the last database lock. Additional subgroup analyses will be presented. Conclusions: Long-term efficacy benefit was observed with N+C over S in this final follow-up from CheckMate 9ER. There were no new safety signals. The results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . FAVN+C; n = 74 FAVS; n = 72 INTN+C; n = 188 INTS; n = 188 PoorN+C; n = 61 PoorS; n = 68 PFS HR (95% CI) 0.67 (0.46–0.97) - 0.63 (0.50–0.80) - 0.36 (0.23–0.56) - mPFS (95% CI), mo 21.4 (12.8–24.6) 12.8 (9.4–16.6) 16.6 (11.3–21.7) 8.5 (6.9–10.4) 9.9 (5.9–17.7) 4.2 (2.9–5.7) 60-mo PFS rate, % 15.1 3.9 12.7 4.7 15.7 0 OS HR (95% CI) 1.08 (0.70–1.66) - 0.86 (0.67–1.11) - 0.49 (0.33–0.74) - mOS (95% CI), mo 53.7 (40.8–70.7) 58.9 (46.1–NE) 47.4 (38.2–55.8) 36.2 (25.7–46.3) 34.8 (21.4–53.4) 10.5 (6.8–20.7) 60-mo OS rate, % 46.3 49.4 41.2 38.2 33.1 12.9 ORR (95% CI), % 66.2 (54.3–76.8) 43.1 (31.4–55.3) 55.9 (48.4–63.1) 27.7 (21.4–34.6) 42.6 (30.0–55.9) 10.3 (4.2–20.1) CR, % 16.2 6.9 15.4 4.8 6.6 1.5 60-mo DOR rate, % a 22.0 NE 19.0 13.0 37.0 0 FAV, IMDC favorable; INT, IMDC intermediate; NE, not estimable; poor, IMDC poor. a Based on pts with objective response.