Association between depth of response (DepOR) and clinical outcomes: Exploratory analysis in patients with previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 9ER.

4501 Background: Among patients (pts) with untreated aRCC in the CheckMate 9ER trial, superior progression-free survival (PFS; hazard ratio HR, 0.56) and overall survival (OS; HR, 0.70) were maintained, and objective response and complete response (CR) rates were doubled for nivolumab plus cabozantinib (N+C) vs sunitinib (SUN) with extended 25.4 mo minimum (32.9 mo median) follow-up. This exploratory analysis evaluated the relationship between DepOR and clinical outcomes in CheckMate 9ER. Methods: Eligible pts received N (240 mg) every 2 weeks plus C (40 mg) once daily or SUN (50 mg once daily; 4 weeks of each 6-week cycle). In this analysis, DepOR subgroups were based on best overall response (blinded independent central review BICR per RECIST v1.1) and best tumor reduction threshold, as follows: CR; partial response subdivided by a tumor reduction of ≥80%–<100% (PR1); ≥60%–<80% (PR2); or ≥30%–<60% (PR3); stable disease (SD); and progressive disease (PD). PFS (per BICR) and OS by DepOR subgroups were analyzed after a 6-mo post-randomization landmark. Treatment-related adverse events (TRAEs) were assessed in DepOR subgroups. Results: Of 323 and 328 pts randomized to N+C or SUN, 236 and 157 pts were progression-free and alive and 293 and 253 pts were alive at the 6-mo landmark and were categorized by DepOR subgroup. Overall, greater proportions of pts receiving N+C had deeper responses vs SUN (CR, PR1, PR2; Table). Deeper responses with N+C were associated with improved 12-mo PFS rate vs SUN for CR (94.9% vs 82.4%), PR1 (81.3% vs 37.5%), and PR2 (72.1% vs 53.2%). In both arms, increasingly deeper response led to better OS outcome; yet OS rates and medians were comparable between arms for CR, PR1, PR2, and PR3 (Table). No meaningful patterns for overall TRAE rates by DepOR subgroup were identified in either arm. Conclusions: In CheckMate 9ER, more pts receiving N+C achieved deeper responses vs SUN. Deeper responses were generally associated with improved PFS and OS. Clinical trial information: NCT03141177. Table: see text