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Obesity linked to improved OS, PFS in advanced kidney cancer
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Obese patients with metastatic renal cell carcinoma had better survival outcomes than lower-weight patients, according to study results published in Journal of Clinical Oncology.
Patients with higher BMI had decreased expression of the fatty acid synthase (FASN) gene, which is associated with worsened survival outcomes in kidney cancer.
Although obesity is an established risk factor for renal cell carcinoma, several studies have linked obesity to lower disease stage and grade at diagnosis, correlating with better outcomes.
Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology and the Kidney Cancer Center at Dana-Farber Cancer Institute, and colleagues sought to observe the clinical and biologic effect of obesity on patients with metastatic renal cell carcinoma.
The researchers identified 1,975 patients in the International Metastatic Renal Cell Carcinoma Database Consortium treated on and off clinical trials with targeted therapies since 2003.
Obese patients (BMI 25) comprised 60% (n = 1,190) of the cohort; the remaining 40% (n = 785) were normal weight or underweight (BMI < 25).
The researchers further analyzed data from an independent validation cohort drawn from prospective phase 2 and phase 3 trials of sunitinib (Sutent, Pfizer), temsirolimus (Torisel, Pfizer) and axitinib (Inlyta, Pfizer). This dataset included 4,657 patients with available BMI data, 61% (n = 2,828) of whom were obese.
Patients from the International Metastatic Renal Cell Carcinoma Database Consortium had a median OS of 21.5 months (95% CI, 20.1-23.3) from the initiation of targeted therapy. Median OS was 25.6 months among obese patients, compared with 17.1 months among patients in lower weight categories (adjusted HR = 0.84; 95% CI, 0.73-0.95).
This favorable association extended to patients with intermediate- (HR = 0.73; 95% CI, 0.62-0.87) and poor-risk disease (HR = 0.8; 95% CI, 0.65-0.97).
The researchers observed similar outcomes in the validation cohort. Obese patients achieved a median OS of 23.4 months, whereas lower weight patients achieved a median OS of 14.5 months (adjusted HR = 0.83; 95% CI, 0.74-0.93).
Researchers also conducted gene expression profiling, including immunohistochemistry straining for the FASN pathway, on a subset of 61 patients from The Cancer Genome Atlas.
Results showed patients with higher BMI had lower FASN gene expression (P = .034), and patients with lower FASN gene expression had a significantly longer median OS (36.8 months vs. 15 months; P = .002).
When researchers conducted immunohistochemistry staining of the International Metastatic Renal Cell Carcinoma Database Consortium cohort, they found that FASN staining positivity occurred more frequently in poor-risk (48%) and intermediate-risk (34%) patients than favorable-risk patients (17%; P = .015 for trend). FASN–negative patients had significantly longer median OS (27.5 months vs. 14.5 months).
The researchers acknowledged potential study limitations, including the exclusive use of BMI to determine obesity status and their inability to perform subset analyses on morbidly obese patients.
Further, the researchers acknowledged their inability to use metabolic biomarkers in the study.
“We demonstrated that patients with high BMI had a more favorable survival outcome than patients with low BMI,” Choueiri and colleagues wrote. “We believe this work provides insights to further explore the biology and ultimately the therapeutic approaches in patients with advanced renal cell carcinoma.” – by Cameron Kelsall
Disclosure: Choueiri reports honoraria and travel expenses from, as well as consultant roles with Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Eisai, Exelixis, Foundation Medicine, Genentech, GlaxoSmithKline, Merck, National Comprehensive Cancer Network, Novartis, Pfizer, Prometheus and UpToDate. He also reports institutional research funding from multiple pharmaceutical companies. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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