A multicenter, open‐label, single‐arm study of anamorelin (ONO‐7643) in patients with cancer cachexia and low body mass index

Abstract

BACKGROUND:Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI). METHODS: This multicenter, open-label, single-arm study enrolled Japanese patients with non-small cell lung cancer or gastrointestinal cancer with cancer cachexia (BMI < 20 kg/m 2 , involuntary weight loss > 2% in the last 6 months, and anorexia). Patients were administered 100 mg of anamorelin once daily for up to 24 weeks. The primary end point was a composite clinical response (CCR) at 9 weeks, which was defined as an increase in body weight of ≥5% from the baseline, an increase of ≥2 points in the score of the 5-item Anorexia Symptom Scale of the Functional Assessment of Anorexia/Cachexia Therapy, and being alive. RESULTS: One hundred two patients were eligible and enrolled. The means and standard deviations for age and BMI were 71.0 ± 8.2 years and 17.47 ± 1.48 kg/m 2 , respectively. The CCR rate at 9 weeks was 25.9% (95% confidence interval [CI], 18.3%-35.3%), which met the primary end point with a lower 95% CI exceeding the prespecified minimum of 8%. Improvements in body weight and anorexia were durable and were accompanied by improvements in patients' global impression of change for appetite/eating-related symptoms and overall condition. Adverse drug reactions occurred in 37 of 101 treated patients (36.6%), with the most common being glycosylated hemoglobin increases, constipation, and peripheral edema. CONCLUSIONS: Anamorelin improved body weight and anorexia-related symptoms in patients with cancer cachexia and a low BMI with durable efficacy and favorable safety and tolerability.

Surgical Prehabilitation in Patients with Gastrointestinal Cancers: Impact of Unimodal and Multimodal Programs on Postoperative Outcomes and Prospects for New Therapeutic Strategies—A Systematic Review

“…Indeed, those studies did not affect the patient’s QoL, muscle strength, and physical performance. In GI cancers, similar results were obtained with an increased appetite and a marginal body weight gain [ 24 , 25 ]. Currently, there is only one multicenter RCT registered in ClinicalTrials.gov (NCT04844970) that evaluates the efficacy and safety of anamorelin in 100 patients with advanced pancreatic cancer.…”

“…Finally, pharmaceutical molecules such as anamorelin could also contribute to prehabilitation programs. This ghrelin receptor agonist with appetite-enhancing effects has recently been shown to increase body weight in malnourished patients with GI cancers [ 24 , 25 ].…”

Efficacy and safety of anamorelin in patients with cancer cachexia: Post‐hoc subgroup analyses of a placebo‐controlled study

“…In the present study, we evaluated appetite using a single question (item 8 of QOL‐ACD). This item was used in the previous clinical trials of anamorelin in Japan with consistent results among the trials 20–22,38 . Therefore, we believe this item provides a reliable assessment of appetite.…”

“…This item was used in the previous clinical trials of anamorelin in Japan with consistent results among the trials. [20][21][22]38 Therefore, we believe this item provides a reliable assessment of appetite.…”

Establishment of a Cell Line Stably Expressing the Growth Hormone Secretagogue Receptor to Identify Crocin as a Ghrelin Agonist

“…It is known that the half-life of ghrelin in the human body is very short [ 7 ], and thus there is an urgent need for potential ghrelin agonists for the development of new adjuvant therapy. Many ghrelin agonists have been proven to be effective in the management of anorexia, sarcopenia, gastrointestinal diseases, and neurodegenerative disorders [ 8 , 9 ]. However, side effects were reported in patients treated with these agonists, including nausea, musculoskeletal pain, heart failure, hyperglycemia, fluid retention, and inhibition of Cytochrome P450 3A4 [ 10 , 11 ].…”