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.

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, >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.