The investigational agent anamorelin significantly increased lean body mass, body weight, total body mass, and fat mass in patients with advanced non–small cell lung cancer (NSCLC) and cachexia, according to Jennifer S. Temel, MD, who presented the results of two phase III studies at the 2015 Palliative Care in Oncology Symposium in Boston.¹

Cancer anorexia/cachexia syndrome develops in up to 70% of patients with advanced cancer and is characterized by decreased appetite and food intake as well as loss of body weight and lean body mass. Patients with this condition frequently experience decreased quality of life, lower chemotherapy tolerance, reduced physical functioning, and worse survival.

“Cachexia is a common condition, especially in patients with advanced NSCLC,” said Dr. Temel, Clinical Director of Thoracic Oncology at Massachusetts General Hospital in Boston. “This condition significantly impacts patients, as well as family members; it is quite distressing for them when their loved one can’t participate in family meals and for them to witness the physical changes associated with cachexia.”

Currently, there are few therapeutic options and no standard of care for the treatment of anorexia/cachexia. “Current treatment options have limited efficacy and potential side effects, such as muscle wasting associated with prolonged use,” she said.

Dr. Temel and her colleagues conducted two international, randomized, double-blind trials (ROMANA 1 and ROMANA 2) evaluating the effect of anamorelin, an orally active, highly selective ghrelin receptor agonist, on cachexia in patients with advanced NSCLC.

Study Design

Patients with inoperable stage III or IV NSCLC and cachexia (≥ 5% weight loss within the prior 6 months or body mass index < 20 kg/m²) were randomly assigned to ROMANA 1 (484 patients) or ROMANA 2 (495 patients). Patients were randomized in a 2:1 fashion to receive 100 mg of anamorelin or matching placebo, administered orally once daily for 12 weeks. All participants were followed for 1 year to assess overall survival.

Coprimary efficacy endpoints were the change in lean body mass and handgrip strength from baseline over 12 weeks. Secondary endpoints included change in body weight, anorexia/cachexia symptoms and fatigue over 12 weeks, and pooled overall survival at 1 year. Exploratory analyses evaluated change in total body mass and fat mass from baseline to 12 weeks.

The majority of study participants had stage IV disease. “The most common NSCLC histology was squamous cell carcinoma, reflecting the fact that this was an internationally conducted trial,” added Dr. Temel.

Statistically Significant Improvements

Patients assigned to anamorelin experienced an increase in lean body mass compared with those assigned to placebo in ROMANA 1 (1.10 of kilogram gain vs –0.44 kg lost, P < .001) and ROMANA 2 (0.75 vs –0.96 kg, P < .001), but no difference in handgrip strength was observed.

Patients assigned to anamorelin had a significant increase in body weight (2.2 vs 0.14 kg, P < .001) and (0.95 vs –0.57 kg, P < .001) and improvement in their anorexia/cachexia symptoms (4.12 vs 1.92, P < .001) and (3.48 vs 1.34, P = .002) in ROMANA 1 and 2, respectively (higher scores are consistent with a lower symptom burden for both of these symptom scales).

“In both ROMANA 1 and 2, even as early as the 3-week time point, there was a statistically significant difference favoring anamorelin in respect to changes in body weight and anorexia/cachexia symptoms,” said Dr. Temel. “These differences were sustained and dramatic throughout the study period.”

Exploratory analysis demonstrated an increase in total body mass (2.87 vs 0.07 kg, P < .001) and (2.04 vs –0.59 kg, P < .001), and fat mass (1.21 vs –0.13 kg, P < .001) and (0.77 vs 0.09 kg, P = .01) for anamorelin vs placebo in ROMANA 1 and 2, respectively.

“At the 9- and 12-week time points in ROMANA 1, there were statistically significant differences favoring patients assigned to anamorelin in respect to lower rates of fatigue, but there were no such differences for patients in ROMANA 2,” she added.

The investigators concluded that anamorelin was effective in improving anorexia/cachexia symptoms in patients with advanced NSCLC. Patients experienced significant increases in lean body mass, body weight, total body mass and fat mass, indicating increased anabolic activity and renewed energy balance. ■

Disclosure: Dr. Temel has received research funding and travel expenses from Helsinn Therapeutics.

Reference

1. Temel J, Currow D, Fearon K, et al: Anamorelin in patients with advanced non-small cell lung cancer and cachexia: Results from the phase III studies ROMANA 1 and 2. 2015 Palliative Care in Oncology Symposium. Abstract 175. Presented October 9, 2015.