Data from two phase III trials presented at ESMO 2014 indicate that anamorelin, a novel selective ghrelin receptor agonist with appetite-enhancing and anabolic activity, improves the appetite and body mass in patients with advanced lung cancer who are suffering cancer anorexia and cachexia, two of the most troubling and distressing symptoms of advanced cancer. In addition to quality of life of patients and family members, these symptoms have an impact on anti-cancer treatment efficacy and toxicity as well as survival.
Symptoms of the so-called wasting syndrome can include a loss of weight and muscles, together with fatigue, weakness, and loss of appetite. The condition is very common in patients with advanced lung cancer and negatively impacts quality of life and prognosis. The current management of this conditionincludes nutritional counseling, resistance training and increase of physical activity, psychosocial support and multimodal symptom control. However, these interventions are limited in their effect, and no pharmacological treatment is available to address the relevant components of the syndrome. In addition to quality of life of patients and family members, the syndrome also has an impact on anticancer treatment efficacy and toxicity as well as survival. Anamorelin aims to address the symptoms by mimicking the effects of the so-called “hunger hormone” ghrelin, which is secreted by the stomach. In the large, randomized controlled ROMANA 1 and 2 trials, the impact of anamorelin on anorexia-cachexia in patients with advanced lung cancer was examined. In these studies, patients with unresectable stage III or IV non-small cell lung cancer (NSCLC) with cachexia were randomized to receive either 100 mg anamorelin or placebo, given orally each day for 12 weeks.
Among the 484 participants in ROMANA 1, those taking anamorelin experienced a median increase in lean body mass of 1,10 kg in 12 weeks, compared to a loss of 0,44 kg for those taking placebo. Body weight increased in the anamorelin-arm by an average of 2,2 kg, compared to 0,14 kg in the placebo-arm of the study. Patient symptoms or concerns regarding anorexia-cachexia, including appetite, also significantly improved over 12 weeks in patients taking anamorelin. The most frequent drug-related adverse events included hyperglycemia and nausea.
In ROMANA 2, a total of 495 participants with advanced NSCLC experienced similar benefits. In fact, the body weight increased by 0,95 kg on average with anamorelin, compared to a loss of 0,57 kg for those receiving placebo and patient symptoms/concerns regarding anorexia-cachexia significantly improved over 12 weeks. Patients receiving anamorelin did not experience improvements in their muscle strength, as measured by hand grip strength. However, it is important to note that this particular test can be difficult to administer in this patient population.
In summary, the ROMANA trials identify anamorelin as a well tolerated drug that improves the troubling symptoms of anorexia and cachexia. As such, this drug has the potential to have an impact on both patients and their families. This is the first anti-cachexia drug for which reports from two placebo-controlled, double blind phase III trials show a consistent effect on different components of the cancer anorexia-cachexia syndrome. However, further data are needed to show whether the increase of muscle mass is accompanied by a gain of fat mass, which would confirm that patients can build reserves while having more appetite.
Temel J, Currow D, Fearon K et al. Anamorelin for the treatment of cancer anorexia-cachexia in NSCLC: results from the Phase 3 studies ROMANA 1 and 2. Presented at ESMO 2014; Abstract 1483O.