anamorelin and Lung-Neoplasms

Anamorelin was approved for production and marketing in Japan on 22 January 2021 for cancer cachexia in non-small-cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer. The authors describe the updates of anamorelin for cancer cachexia in Japan.. Recent evidence showed that anamorelin improved lean body mass, body weight, and appetite in patients with cancer cachexia in clinical practice. Anamorelin does not increase body weight in the severe-weight-loss group in cachectic patients with pancreatic cancer. Several case reports showed that anamorelin can cause cardiac adverse drug reactions. Among the cardiac adverse reactions, fatal arrhythmias should be monitored carefully even if it is the first dose. Anamorelin combined with nutrition, physical activity, and exercise may be more useful than anamorelin alone for treating cancer cachexia. An interim analysis from post-marketing all-case surveillance was performed; however, details have not yet been published. When anamorelin cannot be used for cancer cachexia, Kampo medicines can be considered as an option.. Anamorelin has changed the clinical practice of cancer cachexia in Japan. The authors hope that anamorelin is available for other disease-related cachexia along with appropriate multidisciplinary interventions.

Topics: Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; East Asian People; Humans; Lung Neoplasms; Neoplasms; Pancreatic Neoplasms

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.. 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.. 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.

Topics: Anorexia; Cachexia; Carcinoma, Non-Small-Cell Lung; Humans; Hydrazines; Lung Neoplasms; Neoplasms; Oligopeptides

Cancer anorexia-cachexia syndrome (CACS) is characterized by involuntary weight loss. CACS is commonly observed in advanced non-small-cell lung cancer (NSCLC), and it leads to a poor quality of life (QOL). No effective standard treatment exists for this condition. However, anamorelin has reportedly caused improvement in patients with several cancers.. We conducted a quantitative meta-analysis to explore the efficacy of anamorelin for treating CACS in patients with NSCLC. We systematically searched CENTRAL, MEDLINE, EMBASE, CINAHL, and OvidSP. We pooled the data and calculated and compared total body weight (TBW), lean body mass (LBM), overall survival (OS), hand grip strength (HGS), QOL, and adverse events (AEs) between patients treated with anamorelin (anamorelin group) and those not (placebo group).. Six randomized controlled trials included 1641 patients with NSCLC. Both TBW and LBM were significantly increased in the anamorelin group compared to the placebo group (mean differences [MD] 1.78, 95%CI: 1.28-2.28, p<0.00001; MD 1.10, 95%CI: 0.35-1.85, p=0.004, respectively). The groups showed no difference in OS or HGS (hazard ratio 0.99, 95%CI: 0.85-1.14, p=0.84; MD 0.52, 95% CI: -0.09-1.13, p=0.09, respectively). Anamorelin significantly improved the QOL (standardized MD 0.19, 95%CI: 0.08-0.30, p=0.0006). The frequency of any AEs and grade 3 or 4 AEs were not significantly different between groups (risk ratio[RR] 1.03, 95%CI: 0.95-1.10, p=0.49; RR 0.86, 95%CI: 0.48-1.54, p=0.62).. This analysis demonstrated that anamorelin represents a promising treatment option for CACS in patients with advanced NSCLC.

Topics: Age Factors; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Humans; Hydrazines; Lung Neoplasms; Odds Ratio; Oligopeptides; Quality of Life; Randomized Controlled Trials as Topic; Sex Factors; Treatment Outcome

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.. 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.. 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.

Topics: Animals; Anorexia; Appetite; Cachexia; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase II as Topic; Humans; Hydrazines; Lung Neoplasms; Oligopeptides; Randomized Controlled Trials as Topic; Receptors, Ghrelin

Cachexia, a disorder associated with anorexia, inflammation, and muscle wasting, is frequent in cancer patients. We performed post-hoc analyses of the ONO-7643-04 study to investigate the efficacy and safety of anamorelin in subgroups of Japanese patients with non-small cell lung cancer (NSCLC).. The patients were divided into subgroups by baseline characteristics, including sex, age, body mass index, prior weight loss, performance status (PS), concomitant anticancer therapy, and number of previous chemotherapy regimens. The changes from baseline through to 12 weeks for lean body mass (LBM), body weight, and appetite were calculated. Appetite was evaluated using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD) item 8 score. Responder rates were defined as the maintenance/improvement of LBM (≥0 kg), body weight (≥0 kg), or QOL-ACD item 8 score (≥0) from baseline to all evaluation time points. Safety was evaluated in patients subgrouped by age and PS.. Anamorelin resulted in greater improvements versus placebo in LBM, body weight, and appetite in most subgroups. Anamorelin was also associated with greater LBM, body weight, and appetite responder rates than placebo in nearly all subgroups. Among anamorelin-treated patients, adverse drug reactions (ADRs) tended to be more frequent with increasing age (<65 years, 19.2%; ≥65 to <75 years, 45.9%; ≥75 years, 60.0%) and PS score (PS 0-1, 38.4%; PS 2, 60.0%). The frequency of serious ADRs was 2.7% and 0% in the PS 0-1 and PS 2 subgroups, respectively.. This study of NSCLC patients with cancer cachexia revealed consistent improvements in LBM, body weight, and appetite across most subgroups of anamorelin-treated patients. This study also demonstrated the tolerability of anamorelin regardless of age and PS, with a low incidence of serious ADRs in each subgroup.

Topics: Aged; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasms; Quality of Life

Anorexia is experienced by most people with lung cancer during the course of their disease and treatment. Anorexia reduces response to chemotherapy and the ability of patients to cope with, and complete their treatment leading to greater morbidity, poorer prognosis and outcomes. Despite the significant importance of cancer-related anorexia, current therapies are limited, have marginal benefits and unwarranted side effects. In this multi-site, randomised, double blind, placebo controlled, phase II trial, participants will be randomly assigned (1:1) to receive once-daily oral dosing of 100mg of anamorelin HCl or matched placebo for 12 weeks. Participants can then opt into an extension phase to receive blinded intervention for another 12 weeks (weeks 13-24) at the same dose and frequency. Adults (≥18 years) with small cell lung cancer (SCLC); newly diagnosed with planned systemic therapy OR with first recurrence of disease following a documented disease-free interval ≥6 months, AND with anorexia (i.e., ≤ 37 points on the 12-item Functional Assessment of Anorexia Cachexia Treatment (FAACT A/CS) scale) will be invited to participate. Primary outcomes are safety, desirability and feasibility outcomes related to participant recruitment, adherence to interventions, and completion of study tools to inform the design of a robust Phase III effectiveness trial. Secondary outcomes are the effects of study interventions on body weight and composition, functional status, nutritional intake, biochemistry, fatigue, harms, survival and quality of life. Primary and secondary efficacy analysis will be conducted at 12 weeks. Additional exploratory efficacy and safety analyses will also be conducted at 24 weeks to collect data over longer treatment duration. The feasibility of economic evaluations in Phase III trial will be assessed, including the indicative costs and benefits of anamorelin for SCLC to the healthcare system and society, the choice of methods for data collection and the future evaluation design. Trial registration. The trial has been registered with the Australian New Zealand Clinical Trials Registry [ACTRN12622000129785] and approved by the South Western Sydney Local Health District Human Research Ethics Committee [2021/ETH11339]. https://clin.larvol.com/trial-detail/ACTRN12622000129785.

Topics: Adult; Anorexia; Australia; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Double-Blind Method; Feasibility Studies; Humans; Lung Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Small Cell Lung Carcinoma; Treatment Outcome

Health-related quality of life (HRQoL) measurements from disease-specific tools cannot be directly used in economic evaluations. This study aimed to develop and validate mapping algorithms that predicted EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) utilities from Functional Assessment of Anorexia-Cachexia Therapy (FAACT) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and their common component (Functional Assessment of Cancer Therapy-General-FACT-G) in patients with non-small cell lung cancer cachexia.. Data were collected on five occasions over a 12-week period in two multicenter placebo-controlled trials. EQ-5D-5L utilities were calculated using both English and Dutch value sets. The study sample was divided into development and validation datasets according to patients' geographical residence. Generalized estimating equations were applied to five different sets of independent variables including overall, Trial Outcome Index (TOI), and individual subscales results. The best performing models were selected based on mean absolute error (MAE) and root-mean square error (RMSE).. EQ-5D-5L and FAACT/FACIT-F results were available for 96 patients. The developed algorithms showed a good predictive performance, with acceptable MAE/RMSE and small differences between mean observed and predicted EQ-5D-5L utilities. In FACT-G models, Physical Well-Being had the highest explanatory value, while Emotional Well-Being did not significantly affect the EQ-5D-5L score; Anorexia-Cachexia and Fatigue subscales were highly statistically significant in FAACT and FACIT-F models, respectively, as well as the TOI scores. The Eastern Cooperative Oncology Group status was included as covariate in all models.. The developed algorithms enable the estimation of EQ-5D-5L utilities from three cancer-specific instruments when preference-based HRQoL data are missing.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Cachexia; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Female; Health Status Indicators; Humans; Hydrazines; Lung Neoplasms; Male; Middle Aged; Netherlands; Oligopeptides; Quality of Life; Regression Analysis; Surveys and Questionnaires; United Kingdom

Cachexia, described as weight loss (mainly in lean body mass [LBM]) and anorexia, is common in patients with advanced cancer. This study examined the efficacy and safety of anamorelin (ONO-7643), a novel selective ghrelin receptor agonist, in Japanese cancer patients with cachexia.. This double-blind clinical trial (ONO-7643-04) enrolled 174 patients with unresectable stage III/IV non-small cell lung cancer (NSCLC) and cachexia in Japan. Patients were randomized to daily oral anamorelin (100 mg) or a placebo for 12 weeks. The primary endpoint was the change from the baseline LBM (measured with dual-energy x-ray absorptiometry) over 12 weeks. The secondary endpoints were changes in appetite, body weight, quality of life, handgrip strength (HGS), and 6-minute walk test (6MWT) results.. The least squares mean change (plus or minus the standard error) in LBM from the baseline over 12 weeks was 1.38 ± 0.18 and -0.17 ± 0.17 kg in the anamorelin and placebo groups, respectively (P < .0001). Changes from the baseline in LBM, body weight, and anorexia symptoms showed significant differences between the 2 treatment groups at all time points. Anamorelin increased prealbumin at weeks 3 and 9. No changes in HGS or 6MWT were detected between the groups. Twelve weeks' treatment with anamorelin was safe and well tolerated in NSCLC patients.. Anamorelin significantly increased LBM and improved anorexia symptoms and the nutritional state, but not motor function, in Japanese patients with advanced NSCLC. Because no effective treatment for cancer cachexia is currently available, anamorelin can be a beneficial treatment option. Cancer 2018;124:606-16. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Topics: Aged; Body Composition; Cachexia; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Female; Humans; Hydrazines; Lung Neoplasms; Male; Middle Aged; Oligopeptides

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.. 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).. 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.. 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.. ROMANA 1 (NCT01387269), ROMANA 2 (NCT01387282), and ROMANA 3 (NCT01395914).

Topics: Aged; Cachexia; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Female; Humans; Hydrazines; Lung Neoplasms; Male; Middle Aged; Oligopeptides; Placebos; Receptors, Ghrelin

Cancer cachexia is characterized by decreased body weight (mainly lean body mass [LBM]) and negatively impacts quality of life (QOL) and prognosis. Anamorelin (ONO-7643) is a novel selective ghrelin receptor agonist under development for treating cancer cachexia.. In this double-blind, exploratory phase 2 trial, we examined the efficacy and safety of anamorelin in Japanese patients (n = 181) with non-small cell lung cancer (NSCLC) and cancer cachexia (≥5 % weight loss within the previous 6 months). The participants were randomized into three groups and were administered 50 or 100 mg anamorelin, or placebo, orally every day for 12 weeks. The co-primary endpoints were the changes from baseline over 12 weeks in LBM and handgrip strength (HGS). Secondary endpoints included body weight, QOL, Karnofsky Performance Scale (KPS), and serum biomarkers.. The change in LBM over 12 weeks was 0.55 and 1.15 kg in the placebo and 100-mg anamorelin groups, respectively, but the efficacy of anamorelin in HGS was not detected. The changes in body weight were -0.93, 0.54, and 1.77 kg in the placebo, 50-mg anamorelin, and 100-mg anamorelin groups, respectively. Anamorelin (100 mg) significantly improved KPS and QOL-ACD compared with placebo. Administration of anamorelin for 12 weeks was well tolerated.. This phase 2 study showed that 100 mg anamorelin has promising results in improving lean body mass, performance status, and especially, QOL in patients with cancer cachexia.

Topics: Aged; Cachexia; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Female; Humans; Hydrazines; Lung Neoplasms; Male; Middle Aged; Oligopeptides; Prognosis; Quality of Life

Cancer anorexia-cachexia syndrome (CACS) is common in advanced cancer patients and associated with weight loss, fatigue, impaired quality of life (QoL), and poor prognosis. The goal of this project was to identify the most responsive items from two QoL measures in the ROMANA 2 (NCT01387282) phase III global study evaluating anamorelin HCl in the treatment of non-small cell lung cancer (NSCLC) cachexia: the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Functional Assessment of Anorexia/Cachexia Therapy (FAACT).. In the ROMANA 2 trial, 477 patients with unresectable stage III or IV NSCLC and cachexia were to be enrolled and randomized (2:1) to receive anamorelin HCl or placebo once daily for 12 weeks. All 203 patients who reached the week 12 visit at the time of data analysis were included. Co-primary endpoints were change from baseline in lean body mass and handgrip strength. QoL was a secondary outcome with FACIT-F and FAACT questionnaires administered at baseline and at weeks 3, 6, 9, and 12.. Two 4-item scales (fatigue/activity and appetite/eating) from the FACIT-F and FAACT questionnaires, respectively, demonstrated good internal consistency reliability, validity, and responsiveness (also referred to as the Simplified Evaluation of Fatigue (SEF) and Simplified Evaluation of Appetite (SEA), respectively). The estimated important difference for each scale was 1-2 points.. These brief scales provide the psychometric properties necessary to promote future research in NSCLC patients with CACS. Additional work should examine the clinical utility of these scales and their impact on treatment decision-making.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Appetite; Appetite Stimulants; Cachexia; Carcinoma, Non-Small-Cell Lung; Fatigue; Female; Hand Strength; Health Status Indicators; Humans; Hydrazines; Lung Neoplasms; Male; Middle Aged; Oligopeptides; Placebos; Psychometrics; Quality of Life; Receptors, Ghrelin; Reproducibility of Results; Surveys and Questionnaires; Weight Loss

Topics: Carcinoma, Non-Small-Cell Lung; Electrocardiography; Humans; Hydrazines; Lung Neoplasms; Tachycardia, Ventricular

Objective Anamorelin, a novel selective ghrelin receptor agonist, was approved in Japan for the treatment of cachexia in pancreatic cancer (PC), albeit with limited evidence. This study evaluated the efficacy and safety of anamorelin in PC and examined the impact of the extent of weight loss on the efficacy of anamorelin. Methods We retrospectively investigated consecutive PC patients with cachexia who received anamorelin at our institution between June 2021 and January 2022. Patients were divided into two groups: moderate-weight-loss group (5-10%) and severe-weight-loss group (>10%). The primary outcome was changes in body weight. The secondary outcomes were changes in appetite and laboratory measures as well as treatment-related severe adverse events. Results A total of 24 patients were included (moderate/severe weight loss: 8/16). The moderate-weight-loss group showed significantly more weight gain than the severe-weight-loss group. Improvements in appetite were consistently observed in each weight-loss group. Changes in laboratory markers were not significantly different between groups. Hyperglycemia (four patients) was the most common cause of severe adverse events, followed by abdominal distension, nausea, elevated liver function tests, and bulimia. Conclusion The efficacy of anamorelin was associated with the extent of weight loss. Although anamorelin improved appetite in each weight-loss group, it increased body weight only in the moderate-weight-loss group. Anamorelin was well-tolerated among advanced PC patients, although caution must be practiced when it is used in patients with concomitant diabetes mellitus.

Topics: Anorexia; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasms; Pancreatic Neoplasms; Retrospective Studies

Anamorelin, a ghrelin receptor agonist, has recently been approved for gastric, pancreatic, and colorectal cancer patients with cachexia in Japan. However, only few studies have investigated the predictors of response to anamorelin in clinical settings. Thus, our study aimed to investigate the predictors of the response, in addition to its efficacy and safety.. The clinical outcomes of 20 patients were evaluated during administration. They were divided into two groups based on lean body mass, responders and non-responders, and their clinical characteristics were compared.. The mean ± standard error (SE) variations at 12 weeks in lean body mass and handgrip strength were 2.63 ± 0.79 kg and - 1.53 ± 1.20 kg, respectively. The mean ± SE variations at 8 weeks in fasting blood glucose and hemoglobin A1c were 32.88 ± 13.77 mg/dL and 0.90 ± 0.18%, respectively. Total protein, albumin, transferrin, and prognostic nutritional index at baseline were significantly higher in responders (n = 8) than in non-responders (n = 12), whereas the neutrophil/lymphocyte and C-reactive protein/albumin ratios at baseline were significantly higher in non-responders than in responders.. The study confirmed the efficacy and safety of anamorelin and identified nutritional or systemic inflammatory markers as predictors of anamorelin response in advanced gastrointestinal cancer patients.

Topics: Albumins; Cachexia; Carcinoma, Non-Small-Cell Lung; Gastrointestinal Neoplasms; Hand Strength; Humans; Lung Neoplasms; Retrospective Studies

Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, is an unremitting problem for cancer patients. Anamorelin has become available for cancer-associated cachexia, but early discontinuation is common in clinical practice. This study aimed to explore factors related to the early discontinuation of anamorelin and its relationship to survival.. This prospective, observational study of multimodal clinical practice involved patients who took anamorelin (100 mg) for cancer-associated cachexia at Aichi Medical University Hospital between 14 May 2021 and 31 March 2022. In July 2022, clinical data were extracted from electronic clinical records. Patients who discontinued anamorelin less than 4 weeks after initiation were defined as the early discontinuation group, and their clinical data and survival time were compared with those of the continuation group. This study was approved by the Ethics Committee of the university (approval no. 2021-124).. Worse PS and low PNI were associated with early discontinuation of anamorelin. Longer survival time was observed in the continuation group.

Topics: Aged; Cachexia; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Prospective Studies

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).. 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.. Anamorelin is a drug that stimulates appetite and promotes weight gain. This clinical trial was aimed at determining its efficacy and safety in Japanese cancer patients with a low body mass index and cachexia, a syndrome associated with anorexia and weight loss. Anamorelin was found to improve body weight and anorexia-related symptoms in these patients, and these effects were durable for up to 24 weeks. Moreover, anamorelin was generally well tolerated. These findings suggest that anamorelin is a valuable treatment option for patients with cancer cachexia and a low body mass index.

Topics: Anorexia; Body Mass Index; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Ghrelin; Humans; Hydrazines; Lung Neoplasms; Oligopeptides

Anamorelin hydrochloride (hereinafter referred to as anamorelin) is an orally active, small-molecule drug with a similar pharmacological action to ghrelin, an endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R

Topics: Animals; Cachexia; Carcinoma, Non-Small-Cell Lung; Ghrelin; Humans; Hydrazines; Japan; Lung Neoplasms; Oligopeptides; Rats; Swine; Tablets; Treatment Outcome

Anamorelin is a ghrelin receptor agonist that can be administered orally and thought to improve cancer cachexia by improving appetite and increasing serum insulin-like growth factor-1. Anamorelin was not approved for use in Europe. In contrast, the use of anamorelin for cancer cachexia in four types of cancer (non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer) was approved in Japan on 11 December 2020. Phase 2 trial (ONO-7643-04) for the treatment of patients with non-small cell lung cancer and cachexia resulted in 1.56 kg lean body mass increase assessed by dual-energy X-ray absorptiometry (DXA). Another study for advanced and unresectable gastrointestinal (colorectal, gastric, or pancreatic) cancer showed 1.89 ± 0.36 kg improvement in lean body mass. Skeletal lean body mass assessed by DXA is important for diagnosing sarcopenia and cachexia in Asia. The approval of anamorelin is expected to change clinical practice of cancer cachexia in Japan and hopefully in other countries. In the past, cachexia was rarely diagnosed in Japan, because it was often thought that cachexia meant terminal stage. The dissemination of clinical findings on anamorelin from Japan, as well as the creation of consensus papers and clinical practice guidelines for cachexia in Japan and Asia, will be required to promote international expansion in the future.

Topics: Cachexia; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Humans; Hydrazines; Japan; Lung Neoplasms; Oligopeptides; Pancreatic Neoplasms

Topics: Cachexia; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Ghrelin; Humans; Hydrazines; Lung Neoplasms; Neoplasms; Oligopeptides

Topics: Cachexia; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Ghrelin; Humans; Hydrazines; Lung Neoplasms; Oligopeptides; Palliative Care

Anamorelin (ONO-7643) is an orally active ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-related anorexia/cachexia. It displays both orexigenic and anabolic properties via ghrelin mimetic activity and transient increases in growth hormone (GH). However, increasing GH and insulin-like growth factor-1 in cancer patients raises concerns of potentially stimulating tumor growth. Therefore, we investigated the effect of ghrelin and anamorelin on tumor growth in a murine NSCLC xenograft model.. Female nude mice (15-21/group) with established A549 tumors were administered ghrelin (2 mg/kg i.p.), anamorelin (3, 10, or 30 mg/kg p.o.), or vehicle controls daily for 28 days. Tumor growth, food consumption, and body weight were monitored. Murine growth hormone (mGH) and murine insulin-like growth factor-1 (mIGF-1) were measured in plasma.. Tumor growth progressed throughout the study, with no significant differences between treatment groups. Daily food consumption was also relatively unchanged, while the percentage of mean body weight gain at the end of treatment was significantly increased in animals administered 10 and 30 mg/kg compared with controls (p < 0.01). Peak mGH levels were significantly higher in ghrelin- and anamorelin-treated animals than in controls, while peak mIGF-1 levels were slightly elevated but not statistically significant. All regimens were well tolerated.. These findings demonstrate that neither anamorelin nor ghrelin promoted tumor growth in this model, despite increased levels of mGH and a trend of increased mIGF-1. Together with anamorelin's ability to increase body weight, these results support the clinical development of ghrelin receptor agonist treatments for managing NSCLC-related anorexia/cachexia.

Topics: Animals; Anorexia; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Disease Models, Animal; Eating; Female; Ghrelin; Growth Hormone; Humans; Insulin-Like Growth Factor I; Lung Neoplasms; Mice; Mice, Nude; Receptors, Ghrelin; Weight Gain; Xenograft Model Antitumor Assays