Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 CheckMate 9ER trial.

603 Background: First-line nivolumab plus cabozantinib (N+C) demonstrated superiority over sunitinib (S) with 25.4 mo minimum follow-up (median, 32.9 mo) in patients (pts) with aRCC in the CheckMate 9ER trial. Here, we report survival, response per blinded independent central review (BICR), and safety after 3 y minimum follow-up in all randomized pts and by IMDC risk score. Methods: Pts were randomized 1:1 (stratified by IMDC risk score, tumor PD-L1 expression, region) to N 240 mg flat dose IV Q2W + C 40 mg PO QD vs SUN 50 mg PO for 4 wk (6-wk cycles) until disease progression or unacceptable toxicity (max N treatment, 2 y). Primary endpoint: progression-free survival (PFS) by BICR. Secondary endpoints: overall survival (OS), objective response rate (ORR) by BICR, and safety. Results: In total, 323 pts were randomized to N+C and 328 to S. With 36.5 mo minimum follow-up (median, 44.0 mo), PFS and OS benefits were maintained with N+C vs S in intent-to-treat pts. Median PFS was 16.6 vs 8.4 mo (HR 0.58 [95% CI 0.48–0.71], P < 0.0001) and median OS was 49.5 vs 35.5 mo (HR 0.70 [95% CI 0.56–0.87], P = 0.0014). ORR (95% CI) was higher with N+C vs S (56% [50–61] vs 28% [24–34]), and 12% vs 5% of pts achieved complete response (CR), respectively. Median duration of response was 23.1 vs 15.2 mo for N+C vs S. PFS, OS, and response are reported across prespecified IMDC risk groups in the table. Any-grade treatment-related adverse events (TRAEs) occurred in 97% vs 93% of pts treated with N+C vs S (grade ≥ 3 TRAE, 67% vs 55%). TRAEs led to discontinuation of C only in 10% of pts, N only in 10% of pts, N+C in 7% of pts, N or C in 28% of pts, and S in 11% of pts. Conclusions: After 3 y minimum follow-up, survival and response benefits were maintained with N+C and remained consistent with previous follow-ups. Median OS with N+C improved by 11.8 mo since the previous data cut. Responses with N+C were durable, with higher CR rates with N+C vs S regardless of IMDC risk group. No new safety signals emerged with additional follow-up in either arm. These results continue to support N+C as a first-line treatment for pts with aRCC. Clinical trial information: NCT03141177 . [Table: see text]