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