Anamorelin Increases Lean Body Mass in Patients With Cancer Cachexia
In an integrated analysis of two phase II trials reported in The Lancet Oncology, Garcia et al found that treatment with anamorelin, an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity, produced a gain in lean body mass in patients with cancer anorexia-cachexia syndrome.
Study Details
In the two double-blind studies, 82 patients with advanced or incurable cancer and weight loss ≥ 5% were randomly assigned between June 2005 and October 2006 at 20 U.S. sites to receive anamorelin at 50 mg (n = 44) or placebo (n = 38) once daily for 12 weeks. The primary outcome measure was lean body mass measured by dual-energy x-ray absorptiometry over the 12-week treatment period.
Outcomes
Among the 38 anamorelin recipients and 36 placebo recipients eligible for efficacy analysis, lean body mass increased by a least-squares mean of 1.89 kg (95% confidence interval [CI] = 0.84–2.95 kg) vs a decrease of −0.20 kg (−1.23 to 0.83, difference = 2.09 kg, P = .0006) at 12 weeks. Total body mass was increased by a least-squares mean of 0.48 kg vs a loss of 1.80 kg (P = .0057). There was no difference in change in fat mass (decreases of least-square means of 0.89 vs 1.70, P = .15).
The anamorelin group had a significant improvement in nondominant hand grip strength (P = .014) and in quality of life assessed by Anderson Symptom Assessment Scale (ASAS) total score (P = .029), including improvements in drowsiness, feeling of well-being, nausea, and sleep. However, the significant difference in adjusted ASAS total score was not maintained in confirmatory sensitivity analysis (P = .073).
The most common grade 3 or 4 adverse events irrespective of causality attribution were fatigue, asthenia, atrial fibrillation, and dyspnea (5% each) in the anamorelin group and pneumonia (8%) and anemia, thrombocytopenia, abdominal pain, anxiety, and dyspnea (5% each) in the placebo group.
The investigators concluded: “Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome. These findings support further investigation in this setting.” Anamorelin is currently being assessed in phase III studies (NCT01387269, NCT01387282, and NCT01395914) in patients with non–small cell lung cancer and cancer anorexia-cachexia syndrome.
Jose M Garcia, MD, of Baylor College of Medicine, is the corresponding author for the Lancet Oncology article.
The study was funded by Helsinn Therapeutics (US), Helsinn Healthcare SA. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
