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Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.

ABSTRACT: INTRODUCTION:Cancer anorexia-cachexia syndrome (CACS) is associated with increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin receptor agonist in clinical development for the treatment of CACS in NSCLC. The aim of this review is to summarize preclinical and clinical studies evaluating anamorelin as a potential promising treatment for CACS in NSCLC. AREAS COVERED:Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability of anamorelin for the treatment of CACS in NSCLC were reviewed. Anamorelin administration may lead to increases in food intake, body weight and lean body mass, and a stimulatory effect on growth hormone secretion in NSCLC patients. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. EXPERT OPINION:Targeting ghrelin receptors presents the advantage of potentially addressing multiple mechanisms of CACS simultaneously including appetite, muscle protein balance, adipose tissue metabolism, energy expenditure and inflammation. Clinical data suggest that anamorelin is well tolerated and it effectively increases appetite, body weight and lean mass in patients with advanced NSCLC. Long-term safety remains unknown at this time. The potential synergistic effects of anamorelin with nutritional support or exercise as well as its efficacy/safety in other tumor types are also unknown.

SUBMITTER: Zhang H

PROVIDER: S-EPMC4677053 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.

Zhang Hongjie H Garcia Jose M JM

Expert opinion on pharmacotherapy 20150506 8

<h4>Introduction</h4>Cancer anorexia-cachexia syndrome (CACS) is associated with increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin receptor agonist in clinical development for the treatment of CACS in NSCLC. The aim of this review is to summarize preclinical and clinical studies evaluating anamorelin as a potential promising treatment for CACS in NSCLC.<h4>Areas covered</h4>Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability ...[more]

PMID: 25945893

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Project description:Background:Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities. Patients and methods:ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ?2 after completing 12?weeks (w) on the ROMANA 1 or ROMANA 2 trials (0-12?weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100?mg or placebo once daily for an additional 12w (12-24?weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12-24?weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0-24?weeks). Results:Of the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N?=?345, mean age 62.0?years; placebo, N?=?168; mean age 62.2?years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment-emergent adverse events (TEAEs; 52.2% versus 55.7%), grade??3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia-cachexia symptoms observed in the original trials were consistently maintained over 12-24?weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P?<?0.0001) and improved anorexia-cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P?<?0.05). No significant improvement in HGS was seen in either group. Conclusion:During the 12-24?weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0-24w treatment period, body weight and symptom burden were improved with anamorelin. Clinical trial registration numbers:ROMANA 1 (NCT01387269), ROMANA 2 (NCT01387282), and ROMANA 3 (NCT01395914).

Project description:BackgroundThis is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.ObjectivesTo evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.Search methodsWe sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.Selection criteriaStudies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology.Data collection and analysisTwo independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.Main resultsWe included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.Authors' conclusionsThis review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

Dataset Information

Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.

Publications

Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.

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