Obese patients with metastatic renal cell carcinoma (RCC) were more likely to survive compared to their normal weight counterparts when receiving immune checkpoint inhibitors (ICI), a study has shown.
RCC is the most deadly of the urogenital cancers, and its incidence is increasing. Males are twice as likely as females to develop it.
A team of researchers including Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, conducted an analysis of 735 metastatic RCC patients who received PD-1/L1 immunotherapies.
Those with a BMI of 25 or greater had significantly longer overall survival (OS), with 1-year rates of 79% versus 66% for those with a BMI below that cutoff. This relationship was observed across tumour categories.
“These findings are consistent with the obesity paradox that was previously seen during the VEGF-targeted therapy era,” the team noted.
“Several hypotheses have attempted to explain this clinical observation in RCC,” Choueiri’s team wrote. “Low fatty acid synthase gene expression, which is inversely correlated with BMI, was associated with longer OS in VEGF-treated patients. Transcriptomic analysis suggests that patients with obesity have tumors with increased angiogenesis gene signatures and peritumoral adipose tissues with increased hypoxia, inflammation, and immune cell infiltration signatures.”
In 319 patients with next-generation sequencing technology, there was no difference between groups for tumour mutation burden, at an average 6.8 mutations per megabase for the low and high BMI groups. Genomic alteration frequency analysis also picked up no differences.
Limitations of the study authors included its retrospective nature, incomplete gene-expression profiling, and between-group imbalances. Patients with higher BMI had greater odds of having better performance status and being in more favourable risk groups, had greater odds of having clear cell histology, having had prior nephrectomy, and having received a checkpoint inhibitor as first-line therapy.
Source: MedPage Today
Journal information: AKA Lalani, et al “Assessment of immune checkpoint inhibitors and genomic alterations by body mass index in advanced renal cell carcinoma” JAMA Oncol 2021; DOI: 10.1001/jamaoncol.2021.0019.
