Renal cell carcinoma (RCC) that develops in individuals with a high body mass index (BMI) is associated with better survival after targeted treatment than RCC that develops in those with a low BMI, according to a new study.
The study, led by Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute in Boston, included 1975 RCC patients in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) who received targeted therapy and an external validation cohort of 4657 RCC patients who received targeted treatment in clinical trials.
In the IMDC cohort, median overall survival (OS) following first-line treatment was 25.6 months in patients with a high BMI (25 kg/m2 or higher) compared with 17.1 months in those with a low BMI (less than 25 kg/m2), Dr. Choueiri’s group reported online ahead of print in the Journal of Clinical Oncology. Following second-line therapy, median OS was 16.4 months in the high-BMI group compared with 8.7 months in the low-BMI group. The differences in survival corresponded to a 16% and 42% decreased risk of death among patients with a high BMI.
In the validation cohort, the median OS after first-line treatment was 23.4 months in the high-BMI group compared with 14.5 months in the low-BMI group. After second-line treatment, median OS was 19.8 and 14.9 months, respectively. The survival differences corresponded to a 17% decreased risk of death in the high-BMI group.
In the IMDC cohort, the median time to failure of first-line treatment was 8.1 months in the high-BMI group compared with 5.7 months in the low-BMI group, which corresponded to a 14% decreased risk of primary treatment among patients with a high BMI. In the validation cohort, median progression-free survival times were 8.2 and 5.5 months in the high- and low-BMI groups, respectively, a significant difference that corresponded to an 18% decreased risk of progression in the high-BMI group.
“We demonstrated that patients with high BMI had a more favorable survival outcome than patients with low BMI. This finding is consistent in the first- and second-line settings for all end points examined including OS, even after adjusting for IMDC prognostic criteria and other baseline characteristics.”
The researchers also examined relationship between of fatty acid synthase (FASN) and BMI using specimens from the IMDC biospecimen cohort. FASN gene expression has been shown to be associated with poor prognosis in various tumor types, including RCC, they noted. The investigators used tissue microarrays from 146 patients who received targeted therapy. At the time of analysis, 122 deaths had occurred (84%). FASN immunohistochemistry staining positivity was recorded in 45 (31%) of the 146 patients. The investigators detected FASN positivity more frequently in poor- and intermediate-risk patients than in favorable risk patients. OS was 27.5 months in FASN-negative patients compared with 14.5 months in FASN-positive patients. In adjusted analyses, FASN-positive patients had a 28% increased risk of death versus FASN-negative patients.
As for how obesity could be associated with improved outcomes in patients with mRCC, the researchers cited a previous study suggesting that longer survival among obese patients versus normal-weight patients is due to a less aggressive disease subtype. Dr Choueiri and colleagues said their findings support that hypothesis, “because FASN gene expression was downregulated in obese patients compared with patients with normal BMI, and higher FASN expression was associated with worse survival.”