Abstract 1196
Background
There is currently no circulating biomarker for renal cell carcinoma (RCC). The use of adjuvant sunitinib for RCC after nephrectomy is controversial, and a biomarker could help to select the patients at highest risk for recurrence. Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain can be detected in circulating plasma. We therefore investigated whether KIM-1 is associated with worse outcomes in patients with localized RCC after nephrectomy.
Methods
In the ECOG-ACRIN 2805 (ASSURE) trial, 1943 patients with resected high-risk RCC were randomized 1:1:1 to sunitinib, sorafenib, or placebo. Post-nephrectomy baseline samples from 182 randomly selected patients (9.4% of the study population) was available for this post-hoc biomarker analysis. Samples were analyzed using a previously validated microbead-based assay. Kaplan-Meier and Cox proportional hazards models were used to test for association between circulating KIM-1 and disease free survival (DFS) as well as overall survival (OS). ROC analysis was performed to evaluate test characteristics for KIM-1 in predicting RCC recurrence within 6 months after nephrectomy.
Results
Higher KIM-1 levels were associated with worse DFS and OS after nephrectomy. This association remained independently significant after controlling for pathologic stage, sarcomatoid features, and Fuhrman grade (DFS: HR 1.20 per log increase in KIM-1, 95% CI 1.09-1.33, p < 0.001; OS: HR 1.27 per log increase in KIM-1, 95% CI 1.11-1.45, p < 0.001). These associations were independent of treatment arm. In Kaplan-Meier analysis using KIM-1 quartiles, higher quartiles of KIM-1 were associated with worse DFS and OS (log-rank p = 0.02 for both). Post-nephrectomy KIM-1 was a prognostic marker for disease recurrence within 6 months after nephrectomy (AUC 0.85).
Conclusions
Elevated plasma KIM-1 is associated with worse DFS and OS in patients with resected RCC, and therefore has potential as an adjuvant biomarker. Analysis of larger cohorts to confirm this association is underway.
Clinical trial identification
NCT00326898.
Editorial acknowledgement
Legal entity responsible for the study
ECOG-ACRIN Cancer Research Group (Peter J. O’Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs).
Funding
National Cancer Institute of the National Institutes of Health under the following award numbers: CA180820, CA180794, CA180867, CA189859.
Disclosure
K.T. Flaherty: Officer / Board of Directors: Loxo Oncology; Officer / Board of Directors: Clovis Oncology; Officer / Board of Directors: Strata Oncology; Officer / Board of Directors: Vivid Biosciences; Advisory / Consultancy, Corporate Advisory Board: X4 Pharmaceuticals; Advisory / Consultancy, Corporate Advisory Board: PIC Therapeutics; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Asana; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Fount; Advisory / Consultancy: Aeglea; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Shattuck Labs; Advisory / Consultancy: Arch Oncology; Advisory / Consultancy: Tolero; Advisory / Consultancy: Apricity; Advisory / Consultancy: Oncoceutics; Advisory / Consultancy: Fog Pharma; Advisory / Consultancy, Checkmate, Boston Biomedical, Pierre Fabre, Cell Medica, and Debiopharm.: Others; Advisory / Consultancy: Neon Therapeutics; Advisory / Consultancy: Tvardi; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy: Takeda; Advisory / Consultancy: Verastem. V. Sabbisetti: Non-remunerated activity/ies, Patents on blood KIM-1 is a diagnostic, prognostic and predictive biomarker of RCC: Other. All other authors have declared no conflicts of interest.
Resources from the same session
4506 - Single intravenous preoperative administration of the oncolytic virus Pexa-Vec to prime anti-tumor immunity
Presenter: Adel Samson
Session: Poster Display session 3
Resources:
Abstract
1631 - Randomized phase 2 clinical trial of NY-ESO-1 protein vaccine combined with cholesteryl pullulan (CHP-NY-ESO-1) in resected esophageal cancer patients
Presenter: Shinichi Kageyama
Session: Poster Display session 3
Resources:
Abstract
4244 - T cell repertoire sequencing reveals dynamics of response to dendritic cell vaccine plus dasatinib for checkpoint blockade resistant metastatic melanoma
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
5791 - Ixovex, a novel oncolytic E1B-mutated adenovirus
Presenter: Mohiemen Anwar
Session: Poster Display session 3
Resources:
Abstract
4170 - Anti-CSPG4 DNA vaccination as a promising strategy for the treatment of CSPG4+ tumors: a comparative oncology trial
Presenter: Federica Riccardo
Session: Poster Display session 3
Resources:
Abstract
5780 - Antitumor activity, immunogenicity and safety of a novel PD-1 vaccine in combination with two chimeric HER-2 peptide vaccine in syngeneic Balb/c, C57Bl/6 models and in beagle dogs
Presenter: Pravin Kaumaya
Session: Poster Display session 3
Resources:
Abstract
5860 - Maternal immunization against ALK as a weapon to fight neuroblastoma
Presenter: Giuseppina Barutello
Session: Poster Display session 3
Resources:
Abstract
4720 - Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumors
Presenter: Jason Luke
Session: Poster Display session 3
Resources:
Abstract
5717 - Anti-PD-L1/IL-15 fusion protein generates robust adaptive immune gene signatures in tumors leading to tumor inhibition and memory responses
Presenter: Stella Martomo
Session: Poster Display session 3
Resources:
Abstract
1802 - Evaluation of the anti-tumor efficacy and immune effects of N-809, a novel IL-15 superagonist/anti-PD-L1 bispecific agent
Presenter: Kristin Hicks
Session: Poster Display session 3
Resources:
Abstract