African Americans who develop metastatic renal cell carcinoma have had worse survival historically than whites. With the advent of targeted therapy, the hope is that the gap in survival would be narrowed. However, a new study has shown that survival for African Americans with metastatic renal cell carcinoma continues to be inferior to that of whites in the post–targeted therapy era.¹ The study identified genomic differences between African Americans and whites that may explain this difference.

“Survival for African Americans and Caucasians with metastatic clear cell renal cell carcinoma has improved post targeted therapy between 1998–2004 and 2006–2011. However, over that period, African Americans continued to have inferior survival,” said lead author Tracy L. Rose, MD, of the University of North Carolina at Chapel Hill, who presented these findings at the 2016 Genitourinary Cancers Symposium.

The findings of the study show that African Americans have fewer von Hippel–Lindau (VHL) mutations, are enriched for the clear cell B molecular subtype of renal cell carcinoma, and have less upregulation of hypoxia inducible factor (HIF)-associated pathways (associated with cell division) than whites.

“These molecular features predict for decreased responsiveness to VEGF [vascular endothelial growth factor]-targeted therapies and inferior survival compared with Caucasians. Data from a national database confirm the inferior survival of African Americans compared with Caucasians in the era of targeted therapy, and this is potentially related to underlying differences in tumor biology,” Dr. Rose told listeners.

Study Details

Dr. Rose and coauthors examined 438 patients (19 African Americans, 419 whites) with clear cell renal cell carcinoma from The Cancer Genome Atlas renal cell carcinoma dataset to identify racial differences in somatic mutation rate, molecular subtype, and RNA expression. Significantly fewer African Americans with metastatic renal cell carcinoma were found to have tumors with VHL mutations (17% vs 50% of whites; P = .04). They then validated these findings in another data set of 135 patients with clear cell renal cell carcinoma (10 African Americans, 125 whites).

“We found no racial differences in the frequency of mutations in other genes studied,” Dr. Rose said.

Renal cell carcinoma is divided into two subtypes: clear cell A tumors, associated with improved survival, and clear cell B tumors, associated with worse survival. The African American population with metastatic renal cell carcinoma was enriched for the clear cell B subtype (79% vs 45% for whites; P < .01).

RNA expression revealed upregulation of several HIF-associated pathways (ie, the VEGF receptor axis) in whites compared with African Americans.

Suggestion of Biologic Differences

The authors then identified 35,152 African Americans and whites with stage IV clear cell renal cell carcinoma from the National Cancer Data Base (NCDB) and analyzed survival in two periods: 1998–2004 (pre–targeted therapy era) and 2006–2011 (post–targeted therapy era). Survival improved over time in both racial groups but remained inferior in African Americans for both periods.

Median overall survival in the post–targeted therapy era was 9.2 months for whites vs 6.5 months for African Americans. Three-year survival was 20% vs 14%, respectively. Five-year survival was 11.5% vs 9.1%, respectively.

“In the aggregate, these findings suggest that intrinsic differences [in tumor biology] may contribute to the known disparity in survival between African Americans and Caucasians, and they may confer resistance to VEGF-targeted therapies,” stated Dr. Rose. ■

Disclosure: Dr. Rose reported no potential conflicts of interest.

Reference

1. Rose TL, Krishnan B, Kuykendal AR, et al: Genomic differences and survival in African Americans with metastatic clear cell renal cell carcinoma in the targeted therapy era. 2016 Genitourinary Cancers Symposium. Abstract 504. Presented January 9, 201