ASCO GU 2020: Overall Survival and Independent Review of Response in CheckMate 214 with 42-month Follow-Up: First-Line Nivolumab + Ipilimumab versus Sunitinib in Patients with Advanced Renal Cell Carcinoma
Dr. Tannir then summarized the study design of CheckMate 214, which has been published before. Patients with clear cell advanced RCC were randomized 1:1 to nivolumab 3 mg/kg + ipilimumab 1 mg/kg Q3W×4 and then nivolumab 3 mg/kg Q2W, or sunitinib 50 mg daily for four weeks on, two weeks off. Endpoints were overall survival, objective response rate, and progression-free survival per IRRC using RECIST v1.1 in IP (primary), ITT (secondary), and favorable patients (exploratory).
Dr. Tannir then presented the updated 42-months results. Overall survival remained superior in ITT and IP patients with nivolumab + ipilimumab versus sunitinib. Objective response rate per IRRC was higher and more responses were ongoing with nivolumab + ipilimumab versus sunitinib (68% v 53% [ITT] and 68% v 52% [IP]). More patients achieved a complete response with nivolumab + ipilimumab, and these were ongoing in 86% [ITT] and 84% [IP] of patients. The progression-free survival probability with nivolumab + ipilimumab stabilized after 24 months at 35% in ITT and IP patients, whereas probabilities declined over time with sunitinib. Among favorable patients, while the objective response rate was 29% with nivolumab + ipilimumab versus 54% with sunitinib, more patients achieved a complete response (13% v 6%), and more responses were ongoing (69% v 54%) with nivolumab + ipilimumab versus sunitinib. 94% of complete responses in favorable patients were ongoing with nivolumab + ipilimumab. Overall survival benefits were similar in both arms, and progression-free survival probabilities are stabilizing with nivolumab + ipilimumab and declining with sunitinib in favorable patients. The incidence of any and grade 3–4 treatment-related adverse events were consistent with previous reports, and no new drug-related deaths occurred in either arm.
Dr. Tannir concluded this 42-months update on CheckMate 214 by noting that superior overall survival and objective response rate with nivolumab + ipilimumab versus sunitinib was maintained in ITT and IP patients with extended follow-up. Progression-free survival curves plateaued after 30 months at ~35% with nivolumab + ipilimumab in both ITT and IP patients. A complete response >10% was observed consistently with nivolumab + ipilimumab regardless of risk category, and the majority of all complete responses and partial responses were ongoing with extended follow-up. In the exploratory favorable-risk subgroup, the objective response rate was higher, and the median progression-free survival was longer with the sunitinib, and the difference in overall survival between the two arms remains inconclusive. Incidence of treatment-related adverse events, treatment-related select adverse events, and corticosteroid use declined over time, and no new safety signal emerged with nivolumab + ipilimumab. Overall survival was not impacted in patients who discontinued nivolumab + ipilimumab due to treatment-related adverse events. These results represent the longest follow-up in a Phase III trial of a checkpoint inhibitor combination for first-line treatment of patients with advanced RCC.
Presented by: Nizar M. Tannir, MD, FACP, Department Chair ad interim, Deputy Department Chair, Ransom Horne, Jr. Professorship for Cancer Research, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, Pennsylvania, Twitter: @shekabhishek at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California