Subgroup analysis of ECOG2 patients from ROMANA 2: A phase III study of anamorelin in NSCLC patients with cachexia.

Abstract

6 Background: Cancer anorexia-cachexia syndrome (CACS), often observed in NSCLC patients, is characterized by decreased body weight, mainly lean body mass (LBM), and is associated with worse morbidity and survival. Anamorelin HCl (ANAM), a novel selective ghrelin receptor agonist with appetite-enhancing and anabolic activity, is in development as a treatment of NSCLC CACS. Methods: ROMANA 2 was one of two global, double-blind, Phase III trials assessing ANAM efficacy and safety in NSCLC. Patients with unresectable stage III/IV NSCLC, ECOG 0-2 and cachexia (≥5% weight loss within prior 6 months or BMI <20 kg/m2), were randomized (2:1) to 100 mg ANAM or placebo, given daily orally for 12 weeks. Co-primary endpoints were change from baseline over 12 weeks in LBM (measured by DXA) and in handgrip strength (HGS). Secondary endpoints included change in patient symptoms/concerns regarding anorexia-cachexia and fatigue (via Functional Assessment of Anorexia/Cachexia Treatment [FAACT] and Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F]). Safety assessments included lab values and adverse events (AEs). This pre-specified analysis focused on ECOG2 patients. Results: ROMANA 2 (N=495) enrolled 130 ECOG2 patients (N=41 placebo; N=89 ANAM). Subgroup demographics were balanced: median age= 64 yr, male (81.5%), metastatic (74.6%), and prior weight loss >10% (61.5%). In the overall trial, ANAM significantly increased LBM vs placebo (0.75 vs -0.96 kg; p<0.0001) and improved FAACT over 12 weeks (3.48±0.9 vs 1.34±1.0; p=0.0016); change in HGS was not statistically different. In the ECOG2 subgroup, ANAM also significantly increased LBM (0.45 vs -2.66 kg; p=0.0004); there was a trend towards improvement in FAACT and FACIT-F but this was not statistically significant. In the ANAM arm of the ECOG2 subgroup, the most frequent drug-related AE was hyperglycemia (4.5%), with few (1.1%) drug-related Grade ≥ 3 AEs. Conclusions: ANAM treatment for 12 weeks was well tolerated. In patients with ECOG2 performance status, which represents a more severe/fragile population, ANAM improved LBM, as well as anorexia-cachexia and fatigue symptoms/concerns in advanced NSCLC cachectic patients. Clinical trial information: NCT01387282.