The effect of everolimus on body composition (BC) in patients with metastatic breast cancer (MBC).
Authors: Baka Nadia , Phuong Lisa , Deng Junwen , Patel Janki , Goldman Jessica , Lyudmer Michael , Shamir Stephanie , Alvarez Soto Alvaro , Anampa Mesias Jesus Del Santo 
Published: June 2021

e13026

Background: BC measurement can distinguish adipose tissue distribution, as well as the quantity and quality of muscle. Dysregulation in the mammalian target of rapamycin (mTOR) signaling pathway is associated with obesity and its related diseases. Everolimus (Eve), an mTOR inhibitor, is used in combination with endocrine therapy (ET) in hormone positive, HER2 negative (HR+/HER2-) MBC. However, there is limited data on the effect of Eve on BC. We aim to assess the effect of Eve on BC in patients (pts) with HR+/HER2- MBC. Methods: Pts with HR+/HER2- MBC who received Eve and ET between 2012 and 2019 at our institution were identified. We collected information about breast cancer diagnosis and treatment, weight (wt), body mass index (BMI), and computed tomography (CT). BC measurements; including skeletal muscle area (SMA), skeletal muscle density (SMD), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscle adiposity (MA); were analyzed at the L3 region on CT scans using Tomovision’s SliceOmatic Version 5.0. Total adipose tissue (TAT) was defined as SAT+VAT+MA. To isolate the effect of Eve on BC we also identified a cohort of pts who received ET only. We compared change in wt, BMI, and BC before and after 3 and 6 months of therapy. Wilcoxon signed rank test was used to compare BC parameters. Results: Our study included 42 pts who received Eve plus ET; 43% were Hispanic and 33% were Black. The median number of prior ET and chemotherapy lines were 1 and 0, respectively. The cohort who received ET alone included 63 patients. Median age was 68 years (interquartile range [IQR] 56-74) for the Eve and ET group and 67 years (IQR 55-74) for the ET only group (p = 0.74). Median baseline BMI was 25.8 kg/m2 (IQR 23.1-28.2) for the Eve and ET group and 28.5kg/m2 (IQR 24.2-30.8) for ET only (p = 0.08). Visceral disease was present in 24 (57%) pts on Eve and ET and 41 (65%) pts on ET only (p = 0.54). At month 3 of treatment with Eve and ET, there was a significant decrease in wt (-2.75kg, IQR -4.53-0.40, p < 0.005), BMI (-1.15kg/m2, IQR -1.71-0.14, p < 0.01), SAT (-21.93cm2, IQR -50.13-5.08, p < 0.01), and TAT (-22.34cm2, IQR -69.89-11.98, p = 0.02), which remained statistically significant at month 6 (wt: -5.70kg, IQR –7.75-1.83, p < 0.01; BMI: -2.3kg/m2, IQR -2.83-0.72, p < 0.01; SAT: -43.00cm2, IQR -73.81-10.69, p < 0.01; TAT: -32.56cm2, IQR –92.18-9.61, p = 0.03). These findings were not seen in pts who received ET only at 3 months (wt: 0.00kg, IQR –2.65-2.38, p = 0.99; BMI: 0.00kg/m2, IQR –1.07-0.91, p = 0.94; SAT: -1.82cm2, IQR -26.10-25.15, p = 0.59; TAT: 0.71cm2, IQR -44.39-27.43, p = 0.35), with similar results at 6 months. There were no statistically significant changes in VAT, SMA, SMD, or MA in both groups at 3 or 6 months. Conclusions: Everolimus is associated with decrease in SAT, with no significant change in VAT, SMA, or SMD. Further investigation is required to determine if these changes are associated with disease outcomes or everolimus toxicities.