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09-05-2024 | Underweight | Original Article

The efficacy and safety of anamorelin among patients with diabetes

Authors: Kenju Ando, Tateaki Naito, Satoshi Hamauchi, Keita Miura, Yuichiro Nishibori, Ayumi Tonsho, Suguru Matsuda, Meiko Morita, Motoki Sekikawa, Kosei Doshita, Hiroaki Kodama, Michitoshi Yabe, Noboru Morikawa, Yuko Iida, Nobuaki Mamesaya, Haruki Kobayashi, Ko Ryo, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Haruyasu Murakami, Kentaro Yamazaki, Toshiaki Takahashi

Published in: International Journal of Clinical Oncology | Issue 8/2024

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Abstract

Background

Anamorelin is a selective ghrelin receptor agonist approved for cancer cachexia in Japan. Little is known about predictors of anamorelin efficacy. This study aimed to assess the effect of diabetes on the efficacy and safety of anamorelin in patients with cancer cachexia.

Methods

Medical records of patients with advanced non-small-cell lung, gastric, pancreatic, or colorectal cancer who received anamorelin between January 2021 and March 2023 were retrospectively reviewed. The diabetic (DM) group included patients with a confirmed diagnosis of type 2 diabetes mellitus, random plasma glucose of ≥ 200 mg/dL, or hemoglobin A1c of ≥ 6.5%. The maximum body weight gain and adverse events during anamorelin administration were compared between the DM and non-DM groups. Patients with a maximum body weight gain ≥ 0 kg were classified as the responders.

Results

Of 103 eligible patients, 31 (30.1%) were assigned to the DM group. The DM group gained less weight (median of −0.53% vs. + 3.00%, p < 0.01) and had fewer responders (45.2% vs. 81.9%, p < 0.01) than the non-DM group. The odds ratio for non-response in the DM group was 6.55 (95% confidential interval 2.37–18.06, p < 0.01), adjusted by age and performance status. The DM group had a higher cumulative incidence of hyperglycaemic adverse events (72.2% vs. 6.3%, p < 0.01) and more discontinuations due to hyperglycaemic adverse events (25.8% vs. 4.2%, p < 0.01) than the non-DM group.

Conclusions

Patients with diabetes and cancer cachexia are less likely to gain weight with anamorelin despite a high risk of hyperglycaemic adverse events.
Literature
1.
go back to reference Fearon K, Strasser F, Anker SD et al (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12:489–495CrossRefPubMed Fearon K, Strasser F, Anker SD et al (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12:489–495CrossRefPubMed
2.
go back to reference Temel JS, Abernethy AP, Currow DC et al (2016) Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 17:519–531CrossRefPubMed Temel JS, Abernethy AP, Currow DC et al (2016) Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 17:519–531CrossRefPubMed
3.
go back to reference Katakami N, Uchino J, Yokoyama T et al (2018) Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04). Cancer 124:606–616CrossRefPubMed Katakami N, Uchino J, Yokoyama T et al (2018) Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04). Cancer 124:606–616CrossRefPubMed
4.
go back to reference Hamauchi S, Furuse J, Takano T et al (2019) A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in advanced gastrointestinal cancer patients with cancer cachexia. Cancer 125:4294–4302CrossRefPubMed Hamauchi S, Furuse J, Takano T et al (2019) A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in advanced gastrointestinal cancer patients with cancer cachexia. Cancer 125:4294–4302CrossRefPubMed
5.
go back to reference Iwai N, Sakai H, Oka K et al (2023) Predictors of response to anamorelin in gastrointestinal cancer patients with cachexia: a retrospective study. Support Care Cancer 31:115CrossRefPubMed Iwai N, Sakai H, Oka K et al (2023) Predictors of response to anamorelin in gastrointestinal cancer patients with cachexia: a retrospective study. Support Care Cancer 31:115CrossRefPubMed
6.
go back to reference Takeda T, Sasaki T, Okamoto T et al (2023) Impact of the extent of weight loss before administration on the efficacy of anamorelin in advanced pancreatic cancer patients with cachexia. Intern Med 62:1887–1893CrossRefPubMed Takeda T, Sasaki T, Okamoto T et al (2023) Impact of the extent of weight loss before administration on the efficacy of anamorelin in advanced pancreatic cancer patients with cachexia. Intern Med 62:1887–1893CrossRefPubMed
7.
go back to reference Dev R, Bruera E, Dalal S (2018) Insulin resistance and body composition in cancer patients. Ann Oncol 29(Suppl 2):ii18–ii26CrossRefPubMed Dev R, Bruera E, Dalal S (2018) Insulin resistance and body composition in cancer patients. Ann Oncol 29(Suppl 2):ii18–ii26CrossRefPubMed
8.
go back to reference Tsilidis KK, Kasimis JC, Lopez DS et al (2015) Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 350:g7607CrossRefPubMed Tsilidis KK, Kasimis JC, Lopez DS et al (2015) Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 350:g7607CrossRefPubMed
9.
go back to reference Hirata Y, Nomura K, Senga Y et al (2019) Hyperglycemia induces skeletal muscle atrophy via a WWP1/KLF15 axis. Insight 4:e124952 Hirata Y, Nomura K, Senga Y et al (2019) Hyperglycemia induces skeletal muscle atrophy via a WWP1/KLF15 axis. Insight 4:e124952
10.
go back to reference Chovsepian A, Prokopchuk O, Petrova G et al (2023) Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status. Mol Metab 73:101729CrossRefPubMedPubMedCentral Chovsepian A, Prokopchuk O, Petrova G et al (2023) Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status. Mol Metab 73:101729CrossRefPubMedPubMedCentral
11.
go back to reference ElSayed NA, Aleppo G, Aroda VR et al (2023) 2. Classification and diagnosis of diabetes: standards of care in diabetes-2023. Diabetes Care 46(Suppl 1):S19–S40CrossRefPubMed ElSayed NA, Aleppo G, Aroda VR et al (2023) 2. Classification and diagnosis of diabetes: standards of care in diabetes-2023. Diabetes Care 46(Suppl 1):S19–S40CrossRefPubMed
12.
go back to reference Takayama H, Takiguchi T, Komura N et al (2023) Efficacy and safety of anamorelin in patients with cancer cachexia: Post-hoc subgroup analyses of a placebo-controlled study. Cancer Med 12(3):2918–2928CrossRefPubMed Takayama H, Takiguchi T, Komura N et al (2023) Efficacy and safety of anamorelin in patients with cancer cachexia: Post-hoc subgroup analyses of a placebo-controlled study. Cancer Med 12(3):2918–2928CrossRefPubMed
13.
go back to reference Garcia JM, Polvino WJ (2009) Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers. Growth Horm IGF Res 19:267–273CrossRefPubMed Garcia JM, Polvino WJ (2009) Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers. Growth Horm IGF Res 19:267–273CrossRefPubMed
14.
go back to reference Miyazaki M, Sawada A, Sawamura D et al (2023) Decreased insulin-like growth factor-1 expression in response to mechanical loading is associated with skeletal muscle anabolic resistance in cancer cachexia. Growth Horm IGF Res 69–70:101536CrossRefPubMed Miyazaki M, Sawada A, Sawamura D et al (2023) Decreased insulin-like growth factor-1 expression in response to mechanical loading is associated with skeletal muscle anabolic resistance in cancer cachexia. Growth Horm IGF Res 69–70:101536CrossRefPubMed
15.
16.
go back to reference Suda K, Matsumoto R, Fukuoka H et al (2016) The influence of type 2 diabetes on serum GH and IGF-I levels in hospitalized Japanese patients. Growth Horm IGF Res 29:4–10CrossRefPubMed Suda K, Matsumoto R, Fukuoka H et al (2016) The influence of type 2 diabetes on serum GH and IGF-I levels in hospitalized Japanese patients. Growth Horm IGF Res 29:4–10CrossRefPubMed
17.
go back to reference Honors MA, Kinzig KP (2012) The role of insulin resistance in the development of muscle wasting during cancer cachexia. J Cachexia Sarcopenia Muscle 3:5–11CrossRefPubMed Honors MA, Kinzig KP (2012) The role of insulin resistance in the development of muscle wasting during cancer cachexia. J Cachexia Sarcopenia Muscle 3:5–11CrossRefPubMed
18.
go back to reference Martin A, Gallot YS, Freyssenet D (2023) Molecular mechanisms of cancer cachexia-related loss of skeletal muscle mass: data analysis from preclinical and clinical studies. J Cachexia Sarcopenia Muscle 14:1150–1167CrossRefPubMedPubMedCentral Martin A, Gallot YS, Freyssenet D (2023) Molecular mechanisms of cancer cachexia-related loss of skeletal muscle mass: data analysis from preclinical and clinical studies. J Cachexia Sarcopenia Muscle 14:1150–1167CrossRefPubMedPubMedCentral
19.
go back to reference Heppner KM, Tong J (2014) Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions. Eur J Endocrinol 171:R21–R32CrossRefPubMed Heppner KM, Tong J (2014) Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions. Eur J Endocrinol 171:R21–R32CrossRefPubMed
20.
go back to reference Ohta H, Horii T, Yasu T (2023) Adverse metabolic effects on glucose in patients receiving anamorelin using a japanese claims database. Oncology 101(12):782–785CrossRefPubMed Ohta H, Horii T, Yasu T (2023) Adverse metabolic effects on glucose in patients receiving anamorelin using a japanese claims database. Oncology 101(12):782–785CrossRefPubMed
Metadata
Title
The efficacy and safety of anamorelin among patients with diabetes
Authors
Kenju Ando
Tateaki Naito
Satoshi Hamauchi
Keita Miura
Yuichiro Nishibori
Ayumi Tonsho
Suguru Matsuda
Meiko Morita
Motoki Sekikawa
Kosei Doshita
Hiroaki Kodama
Michitoshi Yabe
Noboru Morikawa
Yuko Iida
Nobuaki Mamesaya
Haruki Kobayashi
Ko Ryo
Kazushige Wakuda
Akira Ono
Hirotsugu Kenmotsu
Haruyasu Murakami
Kentaro Yamazaki
Toshiaki Takahashi
Publication date
09-05-2024
Publisher
Springer Nature Singapore
Published in
International Journal of Clinical Oncology / Issue 8/2024
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-024-02546-8

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