Patterns of progression in patients treated with nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC) in CheckMate 214.

Abstract

313 Background: First-line NIVO+IPI demonstrates superior survival and response benefits in intent-to-treat (ITT) patients (pts) with aRCC after long-term follow-up in the phase 3 CheckMate 214 trial. Data are scarce on tumor relapse and patterns of disease progression with immuno-oncology agents in this setting. This exploratory analysis of CheckMate 214 characterizes patterns of progression with NIVO+IPI vs SUN with 4 years minimum follow-up. Methods: Pts with clear cell aRCC were randomized to NIVO+IPI Q3W×4 followed by NIVO monotherapy Q2W, or SUN QD×4 weeks (6-week cycle). Patterns of progression were characterized in ITT pts and analyzed post hoc using descriptive statistics. Progression patterns were defined by ≥ 20% target lesion growth (T), unequivocal progression of nontarget lesions (NT), and new lesion(s) (NL). Response and progression were assessed per independent radiology review committee via RECIST v1.1. Results: Radiographic progression (RP) was documented in 299/550 (54.4%) ITT pts with NIVO+IPI vs 289/546 (52.9%) with SUN. Among ITT pts with a confirmed response (objective response = 215/550 [39.1%, NIVO+IPI] vs 177/546 [32.4%, SUN]), 71/215 (33.0%) vs 84/177 (47.5%) pts experienced post-response RP with NIVO+IPI vs SUN; 8/59 (13.6%) vs 3/14 (21.4%) progressed after complete response, and 63/156 (40.4%) vs 81/163 (49.7%) progressed after partial response, respectively. The pattern of RP differed between arms (Table). With NIVO+IPI, 106/299 (35.5%) RPs resulted from NL only vs 74/289 (25.6%) with SUN, and this differential was more pronounced in pts with an initial confirmed response (36/71 [50.7%] vs 23/84 [27.4%]). Most NL-only RPs in initial responders occurred in a single organ (34/36 [94.4%] for NIVO+IPI; 20/23 [87.0%] for SUN) with the most common being lymph nodes (11/34 [32.4%]), brain (8/34 [23.5%]), and lung (5/34 [14.7%]) with NIVO+IPI, and lymph nodes (7/20 [35.0%]), brain (4/20 [20.0%]) and adrenal gland (3/20 [15.0%]) with SUN. Additional progression details, baseline characteristics, and key efficacy outcomes in progressors will be reported. Conclusions: Differential patterns of tumor relapse and disease progression were observed after long-term follow up of patients treated with NIVO+IPI vs SUN in CheckMate 214. NL-only progression occurred more often with NIVO+IPI vs SUN, in particular in the subset of pts who progressed post-response. These patterns may have therapeutic implications. Clinical trial information: NCT02231749 . [Table: see text]