Anamorelin Lean Body Mass Benefit Reported For Cachexic NSCLC Patients

Anamorelin treatment increases lean body mass, but not handgrip strength, in advanced non-small-cell lung cancer patients with cachexia

medwireNews: A joint report of the ROMANA 1 and 2 randomised controlled trials suggests that the ghrelin receptor agonist anamorelin may help combat the effects of cachexia in patients with advanced non-small-cell lung cancer (NSCLC).

All the participants of two phase III clinical trials had inoperable stage III or IV disease and at least 5% involuntary weight loss in the past 6 months or a body mass index below 20 kg/m2, the authors explain in The Lancet Oncology.

After 12 weeks of anamorelin 100 mg/day, 323 patients in the ROMANA 1 study had gained a median of 0.99 kg of lean body mass compared with a 0.47 kg reduction for the 161 patients given placebo, a significant difference.

Similarly, the 330 patients randomly assigned to receive daily anamorelin in the ROMANA 2 study had a median gain in lean body mass of 0.65 kg over 12 weeks whereas the 165 placebo-treated patients lost a median of 0.98 kg.

However, the co-primary endpoint of change in handgrip strength did not significantly differ between participants given anamorelin and those treated with placebo in either study.

Subgroup analysis indicated that men in the ROMANA 1 study who received anamorelin were the only patients to achieve a significant benefit for handgrip strength, experiencing a smaller loss than men given placebo, at –0.76 kg versus –2.51 kg.

Nevertheless, patients in both trials given anamorelin had a significant gain in body weight compared with controls, as well as significant improvement in their average anorexia–cachexia symptoms over the 12 weeks. The benefits were identified after 3 weeks and continued to the end of treatment, report Jennifer Temel, from Massachusetts General Hospital Cancer Center in Boston, USA, and co-investigators.

And the drug did not negatively affect survival, with no significant difference after 1 year of follow-up, at 8.9 versus 9.17 months for the pooled anamorelin and placebo groups, respectively.

“Anamorelin represents a safe and effective treatment option for patients with anorexia and cachexia”, the authors say, noting that less than 1% of anamorelin-treated patients discontinued treatment because of side effects.

Diabetes and hyperglycaemia were the most common grade 1 to 4 treatment-related adverse events occurring in at least 10% of patients, but there was less than 5 percentage points difference between the treatment groups, they emphasise. Grade 1 or 2 nausea was the next most common symptom.

Maurizio Muscaritoli, from Sapienza University of Rome in Italy, writes in an accompanying comment that the anorexia symptom improvement “would argue in favour of a positive effect of anamorelin on food intake”, but observes that as food consumption was not measured it is “difficult to ascertain whether improvement in anorexia translated into optimum nutritional intake, capable of effectively sustaining the anabolic boost of anamorelin”.

Ensuring appropriate nourishment might have led to greater gains in lean body mass, he hypothesises, concluding that “the ROMANA 1 and ROMANA 2 trials offer new hopes for more effective therapeutic strategies for cancer cachexia, where the anabolic properties of drugs, exercise, and optimum nutrition should be integrated to produce measurable effects on patients' quality of life and clinical outcomes.”


Temel JS, Abernethy AP, Currow DC, et al. 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; Advance online publication 19 February 2016.  DOI:

Muscaritoli M. Targeting cachexia: we’re on the way. Lancet Oncol; Advance online publication 19 February 2016. DOI:

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