Effect of enobosarm on physical function in cancer patients with < or ≥ 5% weight loss in a phase IIb trial.

Abstract

e19585 Background: Although cachexia has been defined as >5% weight loss, limited data exists on the prevention and treatment of muscle wasting prior to a patient becoming cachectic. Cancer induced muscle wasting can begin early in the course of a patient’s malignancy resulting in decline in physical function and other detrimental clinical consequences including less tolerability to chemotherapy, worse outcomes, and shorter survival - underscoring the importance of diagnosing and treating this condition at an early stage. Methods: We conducted a randomized, double blind, placebo controlled, multi-center study to evaluate the effect of enobosarm on physical function and muscle wasting in cancer patients. Subjects (n=159) were randomized to oral enobosarm or placebo for 16 weeks. Subjects were males >45y and postmenopausal females, with ≥2% weight loss in the 6 months prior to randomization and diagnosed with NSCLC, colorectal cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia or breast cancer. We report on changes in physical function based on weight loss of < or ≥5%in the 6 months prior to randomization. Results: 103 subjects (MITT) had physical function assessed by stair climb at baseline and week 16 with 24% losing <5% weight in the previous 6 months. Distribution of weight loss was similar across genders, however subjects with <5% weight loss were more likely to be ECOG=0 (<5% loss: 46.2%; ≥5% loss: 35.8%). Subjects with ≥5% weight loss had worse physical function at baseline compared to those with <5% loss (p=0.048). A significant improvement in physical function was observed in subjects that received enobosarm regardless of baseline weight loss (<5% loss, p=0.041, ≥5% loss, p<0.001) while subjects that received placebo failed to improve. Conclusions: Enobosarm was generally well tolerated and showed a statistically significant improvement in physical function in cancer subjects regardless of baseline weight loss. These data provide evidence that enobosarm may play an important role in the management of cancer patients by not only treating, but also preventing further decline in physical function and muscle wasting before a patient becomes cachectic.