Anamorelin Efficacy in Non–Small‐Cell Lung Cancer Patients With Cachexia: Insights From ROMANA 1 and ROMANA 2

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 1, 2025

Cancer cachexia presents a significant challenge, but the ghrelin agonist anamorelin shows promise as potential treatment. This study examined whether baseline systemic inflammatory response (SIR) (measured by modified Glasgow Prognostic Score [mGPS]), low BMI or greater weight loss, was associated with differential treatment effect of in people and non-small-cell lung cancer (NSCLC). ROMANA 1 2 were double-blind, placebo-controlled, randomised Phase 3 trials that enrolled inoperable stage III/IV NSCLC (≥ 5% loss within 6 months body mass index [BMI] < 20 kg/m2). Patients 2:1 to 100 mg once daily placebo, for 12 weeks. is post hoc analysis efficacy endpoints (body composition: lean [LBM] fat [FM]), stratified mGPS, measured intent-to-treat pooled population. Seven hundred ninety-five patients had available data. Anamorelin improved (p 0.001) composition parameters (LBM FM, p 0.01) all mGPS groups. In = 2, increased > hand grip strength (HGS) Functional Assessment Anorexia/Cachexia Therapy Subscale (FAACT A/CS). kg/m2 at ≥ 10% prior months, led increases from versus placebo. showed highest improvements LBM 0.001). FM patients, well physical function symptom burden, particularly inflammation, 10%. These results highlight anabolic mechanisms are more effective high-risk NCT identifiers: 1: NCT01387269; 2: NCT01387282.

Language: Английский

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Real‐world safety and effectiveness of anamorelin for cancer cachexia: Interim analysis of post‐marketing surveillance in Japan

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(9)

Published: May 1, 2024

Abstract Background Anamorelin was approved in Japan 2021 to treat cancer cachexia associated with non‐small cell lung, gastric, pancreatic, or colorectal cancers. Post‐marketing surveillance is being conducted evaluate the real‐world safety and effectiveness of anamorelin. Methods This prospective, observational registered all patients who started treatment anamorelin after April 21, 2021. Hyperglycemia, hepatic impairment, conduction disorders, their adverse events related were defined as main specifications. Body weight (BW) appetite assessed Results analysis based on data January 2023. The sets included 6016 4511 patients, respectively. Treatment‐related ≥1% hyperglycemia (3.9%) nausea (2.6%). incidences hyperglycemia, 4.8%, 1.2%, 1.1%, mean changes (standard error [SE]) BW from baseline weeks 3, 12, 24, 52 0.64 (0.05) kg, 1.19 (0.12) 1.40 (0.21) 1.42 (0.39) (SE) Functional Assessment Anorexia/Cachexia Treatment 5‐item Anorexia Symptom Scale total scores 3.2 (0.09), 4.8 (0.18), 5.2 (0.30), 5.3 (0.47), respectively, exceeding clinically meaningful improvement score (2.0 points). Conclusion overall raised no new concerns, although continued caution may be required for nausea. Improvements also observed clinical settings.

Language: Английский

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Editorial to “An extremely wide QRS complex tachycardia induced by anamorelin”

Journal of Arrhythmia, Journal Year: 2024, Volume and Issue: 40(4), P. 786 - 787

Published: June 4, 2024

This is an editorial comment to "An extremely wide QRS complex tachycardia induced by anamorelin." presented Shimojo et al.1 in the current issue of Journal Arrhythmia. Cancer cachexia a multifocal syndrome patients with cancer characterized reduced muscle mass and malnutrition, causing progressive functional disability quality life. Conventional nutritional support cannot completely reverse cachexia, useful pharmacologic therapies for management are limited. Since 2021, anamorelin has been licensed production marketing Japan as therapy cachexia. Anamorelin functions ghrelin-like agonist may stimulate secretion growth hormones appetite activating ghrelin receptor, known hormone release promoting factor receptor type 1a (GHS-R1a). drug interest field several randomized controlled trials have demonstrated efficacy improving total body weight, lean mass, life, refractory compared placebo.2, 3 In all adverse events or serious events, investigators reported no significant differences terms safety.2, However, this exhibited side effects, such conduction disturbance, hyperglycemia, diabetes worsening, hepatic dysfunction; thus, patient selection posttreatment monitoring very important. generally demonstrates inhibitory effect on system because its Na channel-blocking properties. Therefore, electrocardiographic abnormalities, atrioventricular block, tachycardia, bradycardia appear after administration. Additionally, contraindicated heart failure, ischemic disease, severe moderate-to-severe dysfunction. It administered cautiously those history risk QT prolongation disturbances. Periodic electrocardiogram (ECG), pulse, blood pressure measurements warranted The mechanism behind anamorelin's proarrhythmic effects remains unknown, but weak binding sodium channels L-type calcium was revealed.4 Decreased predispose sudden cardiac death, studies arrhythmia suppression that channel blockers increase incidence death. Sodium blockade-induced disturbances cause reentrant arrhythmias excitability gap widening. Arrhytumia, al. case drug-induced anamorelin.1 Healthcare provider should understand although infrequent, reports. increased levels affected CYP3A4, drug-metabolizing enzyme, serum concentrations be drugs inhibit CYP3A4. Nevertheless, concentration alone determine degree intoxication, including abnormalities proarrhythmias, factors beyond antiarrhythmic concentration, electrolytes genetic factors, also play role. appropriate dose prescribed past Some cases not predictable individual susceptibility drug. respond well lower than general effective range, whereas others do even within range. different blocker required exert myocardial function.5 particular, SCN5A gene encodes alpha subunit Nav1.5 responsible phase 0 action potential. Six related polymorphisms (haplotypes; Hap) promoter region gene. Hap B unique Asians, prevalence 24% Japanese population. Patients who at low doses B.5 Hence, Asians might need more observant about responsiveness, especially regarding ECG changes early Finally, causes potentially fatal carefully monitored before blockade mediates anamorelin. associated pathogenesis addition dependence. Further reports clarification mechanisms warranted, expectation can used safely. authors nothing report. declare they competing financial interests personal relationships could appeared influence work paper. None.

Language: Английский

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Early administration of anamorelin improves cancer cachexia in gastrointestinal cancer patients: an observational study

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 3, 2024

Abstract To report the efficacy of anamorelin in patients with colorectal and gastric cancer cachexia those receiving systemic chemotherapy. We retrospectively collected real-world data from diagnosed cancers experiencing who were treated anamorelin. evaluated treatment by measuring improvements appetite body weight (BW) gain. Between June 2021 October 2022, 43 cachexia—23 20 cancer—were Median observation period was 7.3 months. The participants 25 males median age 71 years BMI 19.7. ECOG PS distribution 4, 33, 6 for grades 0, 1, 2, respectively. Seven received supportive care only, while 36 Thirty-four had chemotherapy previously (≤ 2 regimens) nine ≥ 3 regimens. duration 2.8 months; overall survival After weeks, 24 experienced improvement 21 gained weight; after 12 15 weight. Multivariate analysis showed that before second-line correlated gain at weeks. In univariate analysis, weeks improved Early contributes to BW cachexia.

Language: Английский

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Determination of anamorelin concentration in human plasma using a simple high-performance liquid chromatography-ultraviolet detection method

Drug Discoveries & Therapeutics, Journal Year: 2024, Volume and Issue: 18(4), P. 260 - 264

Published: Aug. 24, 2024

Anamorelin, a non-peptide ghrelin analog and growth hormone secretagogue, is novel oral drug used to treat cancer cachexia. Patients with cachexia frequently use several drugs anamorelin substrate of cytochrome P450 (CYP) 3A4; therefore, drug-drug interactions CYP3A4 inhibitors inducers pose clinical problem. In this study, we aimed determine the concentration in human plasma using simple high-performance liquid chromatography-ultraviolet (HPLC-UV)-based method. The analysis involved extracting 200-μL sample protein precipitation solid-phase extraction. Anamorelin was isocratically separated mobile phase consisting 0.5% potassium dihydrogen phosphate (pH 4.5) acetonitrile (61:39, v/v) on Capcell Pack C18 MG II column (250 mm × 4.6 mm) at flow rate 1.0 mL/min monitored detection wavelength 220 nm. calibration curve linear within range 12.5-1,500 ng/mL, coefficient determination 0.9999. intra- inter-day coefficients variation were 0.37-6.71% 2.05-4.77%, respectively. accuracy assay recovery 85.25-112.94% > 86.58%, This proposed HPLC-UV method can be applied settings.

Language: Английский

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Use of anamorelin hydrochloride in a patient with lung cancer-related cachexia undergoing chemoradiotherapy: A case report

Current Problems in Cancer Case Reports, Journal Year: 2024, Volume and Issue: unknown, P. 100322 - 100322

Published: Sept. 1, 2024

Language: Английский

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Anamorelin and Conduction Defects: A Literature Review and Analysis of the Japanese Pharmacovigilance Database

In Vivo, Journal Year: 2024, Volume and Issue: 39(1), P. 404 - 410

Published: Dec. 31, 2024

Cancer cachexia is characterized by weight loss with a specific decrease in skeletal muscle and adipose tissue. In Japan, anamorelin, which has novel mechanism of action, was approved 2021 for the treatment cancer cachexia. However, little information available on its safety routine clinical care, particular occurrence conduction defects as adverse reactions. Therefore, this study evaluated risk time to onset anamorelin-related performing literature review evaluating Japanese pharmacovigilance database.

Language: Английский

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