Anamorelin in cachectic patients with non-small cell lung cancer (NSCLC) and low BMI (< 20 kg/m2): A pooled efficacy data analysis of two phase 3 studies.

10119 Background: Cancer cachexia can be characterized by weight loss or low BMI, and is associated with increased morbidity and reduced survival. ROMANA 1 [NCT01387269; N = 484] and ROMANA 2 [NCT01387282; N = 495]) were randomized, double-blind, phase 3 trials of anamorelin, an oral ghrelin receptor agonist, in NSCLC patients with cachexia. The main outcomes have previously been reported; briefly, over 12 weeks anamorelin was well tolerated and compared with placebo, significantly increased lean and fat mass and improved anorexia/cachexia symptoms, while changes of handgrip strength (HGS) and fatigue were not different. The aim of this analysis was to assess the response to anamorelin specifically in patients with BMI below 20 kg/m2. Methods: Stage III/IV NSCLC patients with cachexia ( ≥ 5% weight loss during prior 6 months or BMI < 20 kg/m2) were randomly assigned (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. A post-hoc pooled analysis of efficacy data from both trials was conducted in patients with BMI < 20 kg/m2 (N = 182) and with BMI ≥ 20 kg/m2(N = 647). Endpoints included changes in lean body mass (LBM), fat mass (FM), HGS, and changes in self-reported anorexia/cachexia concerns and fatigue. Results: Compared with placebo, anamorelin significantly increased LBM both in patients with low BMI (treatment difference: 1.71 kg [95% CI 0.88 – 2.54]) and in those with normal/high BMI (1.47 kg [1.00 - 1.94]) (p < 0.001). Greater increases in FM were observed in the BMI < 20 kg/m2 (1.66 kg [0.86 – 2.46], p < 0.001) than in the BMI ≥ 20 kg/m2 subgroup (0.79 kg [0.30 - 1.28], p = 0.002). There were no treatment differences in HGS. In patients with low BMI, anamorelin significantly improved vs placebo anorexia/cachexia symptoms (5.27 [2.11 - 8.43], p = 0.001) and fatigue (3.94 [0.56 – 7-32], p = 0.023), while these were not significant in patients with BMI ≥ 20 kg/m2(anorexia/cachexia symptoms: 0.91 [(-0.56) - 2.37], p = 0.224; fatigue: (-0.42) [(-2.07) – 1.23], p = 0.616). Conclusions: Anamorelin increased lean and fat mass while improving anorexia/cachexia and fatigue patient-reported outcomes measures in NSCLC patients with cachexia and BMI < 20 kg/m2. Clinical trial information: NCT01387269 and NCT01387282.