ASCO GU 2023: Treatment-Free Survival Outcomes from the Phase II Study of Nivolumab and Salvage Nivolumab + Ipilimumab in Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A)

( In this rapid abstract session, Dr. Michael Atkins presents on Treatment-Free Survival (TFS) outcomes from the Phase II study (HCRN GU16-260-Cohort A) of nivolumab and salvage nivolumab+ipilimumab in patients with advanced renal cell carcinoma (RCC).

As background, immunotherapy (IO) treatment can be associated with prolonged disease control after discontinuation without needing further anticancer therapy. Unfortunately, toxicity from therapy can also persist after cessation. TFS with and without toxicity can characterize survival time. Significant TFS was reported for CheckMate 067 trial in patients (pts) with metastatic melanoma1 and CheckMate 214 trial for pts with aRCC,2 but treatment was often halted for toxicity rather than a pre-defined treatment endpoint. These authors, therefore, sought to assess TFS in the HCRN GU16 260 trial, which was designed to reduce toxicity and to cap immunotherapy duration.3

Data were analyzed from 128 patients (pts) with clear-cell aRCC treated with first-line nivolumab (NIVO) monotherapy for up to 2 years. As part of the protocol, salvage nivolumab/ipilimumab (NIVO/IPI) for up to 1 year was provided to eligible patients with disease progression at any point or stable disease at 48 weeks (28% of pts).

Full study design is listed below:

HCRN GU16-260-Cohort A.jpg

TFS was defined as the area between Kaplan-Meier curves for time from registration to protocol therapy cessation and for time from registration to subsequent therapy initiation or death, estimated from 36-month (mo) mean times. The time on treatment or off treatment with grade 3+ treatment-related adverse events (TRAEs) was also captured.

Baseline characteristics of the 128 patients is summarized below – and median follow-up was 37.7 months.

HCRN GU16-260-Cohort A ASCO GU.jpg

Efficacy results of the trial are shown below, stratified by IMDC risk category.

Overall response was 36%. At 3-years, 68% remained alive and 38.5% were alive and treatment free.

ASCO GU HCRN GU16-260-Cohort A.jpg

He then depicted this graphically for all risk groups (below) and each risk group separately (not shown).

ASCO GU 23 HCRN GU16-260-Cohort A.jpg

The shaded areas depict the various survival states (legend on the right). TFS is in dark blue. These are patients alive without treatment.

The data is provided in table format – and he highlights the those higher grade TRAES being a small subset of those in the TFS category.

ASCO GU 2023 HCRN GU16-260-Cohort A.jpg

The 36-mo mean time on protocol therapy was 11.5 mos (16.0 mos for favorable pts and 9.6 mos for intermediate/poor risk pts). The 36-mo mean TFS for the whole population was 9.4 mos. For favorable risks patients the mean TFS was 12.9 mos, of which TFS with grade 3+ TRAEs was 1.5 mos. For intermediate/poor risk pts, the mean TFS was 8.0 mos, of which TFS with grade 3+ TRAEs was 1.0 mos. At 36 mos, 65.6% of FAV pts and 27.1% of I/P pts were alive and second-line treatment-free.

Based on this data, they concluded that NIVO monotherapy with salvage NIVO/IPI in non-responders is an active treatment approach in treatment-naïve pts with aRCC and results in substantial TFS and toxicity-free TFS. TFS was particularly high in pts with FAV disease, further supporting the use of an immunotherapy-only regimen in this population.

Presented by: Michael B. Atkins, MD, Lombardi Comprehensive Cancer Center, Washington, DC

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023. 


  1. Regan MM, Mantia CM, Werner L, Tarhini AA, Larkin J, Stephen Hodi F, Wolchok J, Postow MA, Stwalley B, Moshyk A, Ritchings C, Re S, van Dijck W, McDermott DF, Atkins MB. Treatment-free survival over extended follow-up of patients with advanced melanoma treated with immune checkpoint inhibitors in CheckMate 067. J Immunother Cancer. 2021 Nov;9(11):e003743. doi: 10.1136/jitc-2021-003743. PMID: 34799400; PMCID: PMC8606772.
  2. Regan MM, Jegede OA, Mantia CM, Powles T, Werner L, Motzer RJ, Tannir NM, Lee CH, Tomita Y, Voss MH, Plimack ER, Choueiri TK, Rini BI, Hammers HJ, Escudier B, Albiges L, Huo S, Del Tejo V, Stwalley B, Atkins MB, McDermott DF. Treatment-free Survival after Immune Checkpoint Inhibitor Therapy versus Targeted Therapy for Advanced Renal Cell Carcinoma: 42-Month Results of the CheckMate 214 Trial. Clin Cancer Res. 2021 Dec 15;27(24):6687-6695. doi: 10.1158/1078-0432.CCR-21-2283. Epub 2021 Nov 10. PMID: 34759043; PMCID: PMC9357269.
  3. Atkins MB, Jegede OA, Haas NB, McDermott DF, Bilen MA, Stein M, Sosman JA, Alter R, Plimack ER, Ornstein M, Hurwitz M, Peace DJ, Signoretti S, Denize T, Cimadamore A, Wu CJ, Braun D, Einstein D, Catalano PJ, Hammers H. Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A). J Clin Oncol. 2022 Sep 1;40(25):2913-2923. doi: 10.1200/JCO.21.02938. Epub 2022 Apr 20. PMID: 35442713; PMCID: PMC9426835.