Racial Differences in Clinical Outcomes for Metastatic Renal Cell Carcinoma Patients Treated With Immune-Checkpoint Blockade

Abstract

BackgroundImmune-checkpoint-inhibitors (ICIs) have become the cornerstone of metastatic renal-cell-carcinoma (mRCC) therapy. However, data are limited regarding clinical outcomes by race. In this study, we compared the real-world outcomes between African American (AA) and Caucasian mRCC patients treated with ICIs.MethodsWe performed a retrospective study of 198 patients with mRCC who received ICI at the Emory Winship Cancer Institute from 2015-2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) defined as a complete or partial response maintained for at least 6 months per response evaluation criteria in solid tumors version 1.1. Univariate and multivariable analyses were carried out for OS and PFS by Cox proportional-hazard model and ORR by logistical-regression model. Descriptive statistics compared rates of immune-related adverse events (irAEs) and non-clear-cell-RCC (nccRCC) histology were assessed using Chi-square test.ResultsOur cohort was comprised of 38 AA and 160 Caucasian patients. Most were diagnosed with clear-cell-RCC (ccRCC) (78%) and more than half received (57%) PD-1/PD-L1 monotherapy. Most patients were intermediate or poor-risk groups (83%). Comparing to Caucasians, our AA cohort contained more females and nccRCC cases. Kaplan-Meier method showed AAs had no statistically different median OS (17 vs 25 months, p=0.368) and PFS (3.1 vs 4.4 months, p=0.068) relative to Caucasian patients. On multivariable analysis, AA patients had significantly shorter PFS (HR=1.52, 95% CI: 1.01-2.3, p=0.045), similar ORR (OR=1.04, 95% CI: 0.42-2.57, p=0.936) and comparable OS (HR=1.09, 95% CI: 0.61-1.95, p=0.778) relative to Caucasians.ConclusionsOur real-world analysis of ICI-treated mRCC patients showed that AAs experienced shorter PFS but similar OS relative to Caucasians. This similarity in survival outcomes is reassuring for the use of ICI amongst real-world patient populations, however, the difference in treatment response is poorly represented in early outcomes data from clinical trials. Thus, the literature requires larger prospective studies to validate these findings.

Genomic ancestry in kidney cancer: Correlations with clinical and molecular features

“…TCGA analyses have indicated a lower rate of somatic VHL and PBRM1 in AFR patients compared with EUR patients, with a continuous trend based on the size of GA fraction of these ancestries. 9,27 In our ccRCC cohort, we similarly found a lower numeric frequency of VHL (50%) and PBRM1 (17%), yet identified a statistically significant enrichment of BAP1 (50% in AFR, 17% in EUR, 17% in the total cohort). With the limited sample size reported here, validating this finding in larger and more diverse data sets including all ethnicities is needed.…”

“…Unlike other reports of Asian patients that demonstrate a comparable frequency in germline alterations in patients with RCC, 25,26 our rate of germline alterations in EAS (7%) and SAS (0%) was low. TCGA analyses have indicated a lower rate of somatic VHL and PBRM1 in AFR patients compared with EUR patients, with a continuous trend based on the size of GA fraction of these ancestries 9,27 . In our ccRCC cohort, we similarly found a lower numeric frequency of VHL (50%) and PBRM1 (17%), yet identified a statistically significant enrichment of BAP1 (50% in AFR, 17% in EUR, 17% in the total cohort).…”

“…Prior reports using self-reported racial data have shown lower gene expression rates related to vascular endothelial growth factor pathways, which may predict treatment-related outcomes. 7,16,27 31,32 ), these signature differences raise implications for disease pathogenesis and sensitivity to therapeutics targeting the angiogenesis/HIF axis and immune checkpoint blockade.…”

“…Molecular signatures based on gene expression data have been shown to correlate with treatment responses, 19,20 and given that different signatures have enrichment of PBRM1 and BAP1 tumors, we posited that corresponding variances in molecular signatures would exist across GA groups. Prior reports using self‐reported racial data have shown lower gene expression rates related to vascular endothelial growth factor pathways, which may predict treatment‐related outcomes 7,16,27 . Given differences in somatic VHL across ancestry and limited transcriptomic data in this cohort, we interrogated the TCGA and applied contemporary immune deconvolution techniques to examine immune infiltration, metabolomic, and relevant myeloid and angiogenesis‐related signatures.…”

Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta‐analysis

“…Expression levels of these several suppressive mediators were high in the East Asians SCLC cohort 76 . Second, it cannot be excluded that economic, social, and healthcare access may influence the choice of treatment modality 80 . Third, differences in sample size may be the cause of this results, with generally smaller numbers of Asians in the included studies 8,33,35,36 .…”