An overview of anamorelin as a treatment option for cancer-associated anorexia and cachexia

ABSTRACT

Introduction

Cancer cachexia is a complex multifaceted syndrome involving functional impairment, changes in body composition, and nutritional disorders. The treatment of cancer cachexia can be based on these three domains of the syndrome. Phase II and III trials of anamorelin, a ghrelin mimetic agent, have been shown to increase body weight in patients with cancer cachexia, mainly by increasing muscle and fat mass. Anamorelin has been shown to improve anorexia scores.

Areas covered

This review aims to outline the effect of anamorelin on body composition and functional parameters as well as to discuss the clinical importance of these alterations in patients with cancer cachexia.

Expert opinion

To date, there is no treatment approved to enhance body composition and functional parameters in patients with cancer cachexia. Anamorelin, the most advanced therapy to treat cachexia, has not yielded convincing results in all aspects of the syndrome. In particular, no effect has been noted on physical function and long-term survival. Along with these essential improvements for future interventions with anamorelin, subsequent studies must address other etiologies of cancer, rather than non-small cell lung cancer, and add complementary therapies, such as exercise training and nutritional interventions, in an attempt to overcome cancer cachexia.

KEYWORDS:

• Anamorelin
• cachexia
• ghrelin
• muscle strength
• muscle wasting
• sarcopenia

Article highlights

• The impact of ghrelin, known as the hunger hormone, on stimulating appetite and increasing energy intake has encouraged the development of a synthetic agent to counteract anorexia and body weight loss in patients with cancer cachexia;

• Anamorelin, a selective ghrelin-receptor agonist administered orally, has demonstrated in phase II–III clinical trials an improvement in body weight (~2-3 kg), composed of gains in lean body mass (~1-2 kg) and fat mass (~1 kg), as well as greater anorexia-cachexia scores in patients with non-small cell lung cancer and cachexia. Across the trials, the most effective dose of anamorelin that has shown these benefits were 100 mg administered daily;

• Although the mechanism of action is still unknown, anamorelin may promote these adaptations in body composition through an increase in the release of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Anamorelin, just like ghrelin, may also operate at a central level by improving the balance between orexigenic and anorexigenic pathways;

• Anamorelin has not demonstrated any effect on enhancing muscle strength assessed by handgrip strength or muscle endurance evaluated by the 6-minute walking test. Anamorelin did not improve the survival time of patients with cancer cachexia;

• The main adverse events related to the administration of anamorelin were hyperglycemia and gastrointestinal disorders, including nausea, vomiting, and constipation;

• Future interventions with anamorelin should incorporate additional therapies, such as exercise training and nutrition, to evaluate if the combined therapy can optimize the gains in muscle mass and muscle strength in patients with cancer cachexia.

Declaration of interest

S von Haehling has been a paid consultant and/or received fees for lectures from Bayer, Boehringer Ingelheim, BRAHMS/Thermo Fisher, Chugai Pharma, Grünenthal, Helsinn, Novartis, Pharmacosmos, Respicardia, Roche, Servier, and Vifor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The preparation of this manuscript was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001 and by the German Center for Cardiovascular Research (DZHK). GWPD Fonseca is supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 148758/2016-9).