ORLANDO—Body mass index (BMI) predicts survival and overall response (ORR) rates in patients with metastatic clear cell renal cell carcinoma, according to authors of an external validation data analysis (Abstract 405) presented during the 2015 Genitourinary Cancers Symposium.1
“We validated BMI as an independent prognostic factor for improved survival in metastatic renal cell carcinoma (mRCC),” reported lead study author Laurence Albiges, MD, PhD, of the Dana-Farber Cancer Institute in Boston, MA. “Given that this finding was observed in clear cell RCC only, we hypothesize that lipid metabolism may be modulated by the fat laden tumors cells.”
FASN gene expression was associated with overall survival (OS) in one of the two cohorts analyzed, and the authors said the role of fatty acid metabolism in mRCC demands further exploration.
“BMI is associated with OS independently of FASN,” however, Dr. Albiges reported.
The authors sought to shed light on the so-called obesity paradox. “Obesity is a risk factor for renal cell carcinoma (RCC) and a poor prognostic factor across many tumor types,” Dr. Albiges explained.
“However, reports have suggested that RCC developing in an obesogenic environment may be more indolent. We recently reported on the favorable impact of BMI on survival in the International mRCC Database Consortium (IMDC). The current work aims to externally validate this finding and characterize the underlying biology.”
The study authors analyzed data from patients with mRCC who had participated in Pfizer-sponsored phase 2 and 3 clinical trials of targeted therapy during 2003 through 2013, to determine the associations between BMI and OS. .
High-BMI (25 kg/m2 or higher) was associated with significantly longer OS (median OS: 25.6 months vs 17.1 months in patients with lower BMI (less than 25 kg/m2); HR=0.84, 95% CI: 0.73-0.95; P=0.0079).
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“Additionally, we analyzed metastatic pts from the clear cell RCC cohort of TCGA [The Cancer Genome Atlas] dataset to correlate the expression of Fatty Acid Synthase (FASN) with BMI and OS,” Dr. Albiges said.
At the time of initiation of targeted therapy (TT), 1,829 (39%) patients in that external validation cohort were normal or underweight (BMI <25 kg/m2) and 2,828 (61%) were overweight or obese (BMI ≥25 kg/m2), Dr. Albiges reported. In multivariate analyses, the high BMI group had a longer median OS (23.4 months) than the low BMI group (14.5 months; hazard ratio [HR]=0.83; 95% CI: 0.743-0.925; P=0.0008).
High-BMI patients also had better PFS (HR=0.821, 95% CI 0.746-0.903; P<0.0001) and ORR (odds ratio=1.527, 95% CI: 1.258-1.855; P<0.001).
“These results remain valid when stratified by line of therapy,” noted Dr. Albiges. “When stratified by histological subtype, the favorable outcome associated with high BMI was only observed in clear cell RCC.”
Toxicity did not differ between BMI groups.
“FASN staining in the IMDC cohort is ongoing to better investigate the obesity paradox in mRCC,” Dr. Albiges reported.
- Albiges L, Hakimi AA, Lin X, et al. The impact of Body Mass Index (BMI) on outcomes of patients with metastatic renal cell carcinoma treated with targeted therapy: An external validation data set and analysis of underlying biology from The Cancer Genome Atlas. 2015 Genitourinary Cancers Symposium. Abstract 405.