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

Temel, Jennifer S.; Abernethy, Amy Pickar; Currow, David C.; Friend, John; Duus, Elizabeth Manning; Yan, Ying; Fearon, K. C. H.

doi:10.1016/s1470-2045(15)00558-6

Cited by 517 publications

(497 citation statements)

References 30 publications

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“…It has also been shown that physical performance is not solely dependent on muscle mass but also muscle strength 22, 39. Muscle strength, in turn, is reported to be independently associated with muscle radiodensity,40 and in accordance with our findings, greater muscular fat infiltration is found to increase the risk of immobility in older men and women 41…”

Section: Discussionsupporting

confidence: 90%

“…Treatments that will enhance muscle mass or at least slow its depletion, improve strength, and enhance the capacity for independent functioning are therefore needed. Nutritional supplements that are able to generate an anabolic response40 and drugs, for example Anamorelin,41 have demonstrated effects in the prevention and treatment of muscle loss in NSCLC. In future studies, it would be of interest to further investigate these effects as well as combine them with physical activity.…”

Section: Discussionmentioning

confidence: 99%

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Muscle mass and association to quality of life in non‐small cell lung cancer patients

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Sjøblom

Wentzel‐Larsen

et al. 2017

J cachexia sarcopenia muscle

121

137

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BackgroundCancer wasting is characterized by muscle loss and may contribute to fatigue and poor quality of life (QoL). Our aim was to investigate associations between skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) and selected QoL outcomes in advanced non‐small cell lung cancer (NSCLC) at diagnosis.MethodsBaseline data from patients with stage IIIB/IV NSCLC and performance status 0–2 enrolled in three randomized trials of first‐line chemotherapy (n = 1305) were analysed. Associations between SMI (cm2/m2) and SMD (Hounsfield units) based on computed tomography‐images at the third lumbar level and self‐reported physical function (PF), role function (RF), global QoL, fatigue, and dyspnoea were investigated by linear regression using flexible non‐linear modelling.ResultsComplete data were available for 734 patients, mean age 65 years. Mean SMI was 47.7 cm2/m2 in men (n = 420) and 39.6 cm2/m2 in women (n = 314). Low SMI values were non‐linearly associated with low PF and RF (men P = 0.016/0.020, women P = 0.004/0.012) and with low global QoL (P = 0.001) in men. Low SMI was significantly associated with high fatigue (P = 0.002) and more pain (P = 0.015), in both genders, but not with dyspnoea. All regression analyses showed poorer physical outcomes below an SMI breakpoint of about 42–45 cm2/m2 for men and 37–40 cm2/m2 for women. In both genders, poor PF and more dyspnoea were significantly associated with low SMD.ConclusionsLow muscle mass in NSCLC negatively affects the patients' PF, RF, and global QoL, possibly more so in men than in women. However, muscle mass must be below a threshold value before this effect can be detected.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Muscle mass and association to quality of life in non‐small cell lung cancer patients

Bye

Sjøblom

Wentzel‐Larsen

et al. 2017

J cachexia sarcopenia muscle

121

137

View full text Add to dashboard Cite

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“…Moreover, an increased circulating acyl-ghrelin levels in response to dietary restriction seems to play a causative role in weight regain and recidivism after diet-induced weight loss 67 and in patients with Prader-Willi syndrome (PWS), in whom high ghrelin levels are suggested to cause hyperphagia and weight gain 68 . In light of the weight-promoting effects of acyl-ghrelin, a novel ghrelin-receptor agonist anamorelin, is being trialled to assess the safety and effectiveness for the treatment of patients with cancer anorexia and cachexia 69 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Monteiro

Batterham

2017

Gastroenterology

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The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight-reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 (GLP-1) highlights the therapeutic potential of gut-derived signals acting via non-physiological mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage GI signals in order to treat obesity.

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“…There have been two large phase III, double blind placebo-controlled trials of anamorelin in patients with cachexia resulting from unresectable lung cancer. The two studies included a combination of more 900 patients and reported improvement in body weight and anorexia with anamorelin but no improvement in overall survival or strength [51]. Hopefully, pharmacologic interventions will follow a better understanding of the exact mechanism of sarcopenia in patients with HNSCC undergoing CTRT.…”

Section: Main Textmentioning

confidence: 99%

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

2016

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Background: Concurrent chemotherapy and radiation (CTRT) improves disease-free survival in locally advanced head and neck cancer but is associated with numerous acute and chronic toxicities resulting in substantial alterations in body mass and composition. We aim to summarize the current evidence on body composition changes experienced by patients undergoing CTRT, examine the impact of these changes on clinical outcomes and address potential interventions aimed at mitigating the loss. Main Body: Loss of 20 % of pre-CTRT weight predicts poorer treatment tolerance and 30-day mortality. While clinical practice focuses on body weight, emerging data indicates that CTRT causes profound adverse changes in lean body mass (sarcopenia). Higher prevalence of sarcopenia predicts poorer disease-free survival as well as overall survival, lower quality of life and functional performance. The magnitude of CTRT-induced sarcopenia is the equivalent to that observed in a decade of aging in a healthy adult. Alterations in body composition are only explained, in part, by decreased caloric intake; other significant predictors include body mass index, stage, and dysphagia. Lifestyle interventions aimed at preventing loss of whole-body and especially lean mass include nutritional counseling, nutritional supplements, dietary supplements and exercise training. Personalized nutritional counseling has been associated with improvement in quality of life, while the benefits of feeding tube placement are inconsistent. There are inconsistently reported benefits of resistance training in this population. Conclusion: Patients with head and neck cancer undergoing CTRT therapy experience dramatic shifts in body composition, including sarcopenia, which can negatively impact clinical outcomes. Efforts to understand the magnitude, clinical importance and mechanisms of sarcopenia are needed to inform a more personalized approach to mitigating the body composition changes associated with CTRT.

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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

Cited by 517 publications

References 30 publications

Muscle mass and association to quality of life in non‐small cell lung cancer patients

Muscle mass and association to quality of life in non‐small cell lung cancer patients

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

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