Patients in one phase III trial gained 2.4 pounds of lean body mass during 12 weeks of treatment with anamorelin, and those in the second trial had an average increase in lean body mass of 1.65 pounds.
David Currow, BMed, MPH
Patients with advanced lung cancer had improved appetite, less weight loss, and a significant increase in lean body mass when treated with a ghrelin agonist, two randomized trials showed.
Patients in one phase III trial gained 2.4 pounds of lean body mass during 12 weeks of treatment with anamorelin, and those in the second trial had an average increase in lean body mass of 1.65 pounds. Placebo groups in both trials lost lean mass.
Neither of the trials demonstrated improvement in the co-primary endpoint of hand-grip strength among patients randomized to anamorelin, investigators reported at the 2014 ESMO Congress meeting held in Madrid, Spain.
“The benefits observed in these two studies are consistent and broad, addressing the critical issues of reduction in lean body mass, reduced body weight, diminished appetite, and patients’ symptoms and concerns related to cancer anorexia-cachexia,” said David Currow, BMed, MPH, a professor of palliative and supportive services at Flinders University in Adelaide, Australia.
Anorexia and cachexia, or wasting syndrome, are common adverse effects of patients with advanced cancer. It is characterized by loss of muscle mass, decreased nutritional intake, metabolic and inflammatory alterations driven by active cancer disease, and decreased physical and psychosocial function. In particular, the condition affects a large proportion of patients with advanced lung cancer.
Anamorelin mimics and stimulates the activity of ghrelin, a protein that induces the release of growth hormone. Ghrelin stimulates multiple pathways that regulate body weight, lean body mass, appetite, and metabolism, said Currow.
The ghrelin receptor agonist was evaluated in two phase IIII randomized trials involving patients with unresectable stage III/IV non-small cell lung cancer. Eligibility criteria for the two trials included cachexia (associated with ³5% of body weight within the previous 6 months) or a body mass index <20 kg/m2.
The ROMANA 1 trial involved 484 patients and the ROMANA 2 trial had a 495-patient study population. In both trials, patients were randomized to anamorelin 100 mg/d or placebo and followed for 12 weeks. Patients could continue chemotherapy during the trial, but not initiate systemic therapy, and they could receive maintenance chemotherapy.
Both trials had co-primary endpoints of change in lean body mass from baseline to 12 weeks (as assessed by dual x-ray absorptiometry), and change in hand-grip strength in the nondominant hand. Secondary endpoints consisted of change in body weight and quality of life and overall survival.
Collectively, the trials involved investigators in North America, Europe, Asia, Australia, New Zealand, and Australasia.
The results showed the treatment groups in both trials were similar. Most patients in both arms were receiving some form of systemic or radiation therapy. In ROMANA 1, 14% of patients in the placebo arm and 11% in the anamorelin received no cancer therapy during the study. In ROMANA 2, 24.2% and 22.4% of placebo and anamorelin patients received no cancer therapy during the trial.
When the trials ended, the data showed increased lean body mass in the anamorelin arms of both trials and loss of lean mass in the placebo groups. The differences in favor of the anamorelin easily achieved statistical significance (P <.0001 in both studies).
Patients in ROMANA 1 had an average weight gain of about 5 pounds versus less than a half pound in the placebo arm (P <.0001). In ROMANA 2, weight gain averaged a little more than 2 pounds with anamorelin, whereas body weight declined by more than a pound in the placebo group (P <.0001)
Quality-of-life assessment showed that patients treated with anamorelin had significant lessening anorexia-cachexia symptoms and concerns (P = .0004).
Hand-grip strength did not improve with anamorelin in either trial. In ROMANA 1, hand-grip strength decreased to a lesser degree with anamorelin as compared with placebo, whereas hand-grip strength in ROMANA 2 declined slightly more in the anamorelin group than in the placebo group.
Grade 2 or greater adverse events occurred in 10% to 15% of patients treated with anamorelin and 8% to 10% with placebo. Grade 3/4 adverse events occurred in 1% to 2.5% of patients in the anamorelin and placebo groups.
The most frequent adverse events associated with anamorelin were hyperglycemia (4% to 5%) and diabetes (1% to 2%).
Overall survival has yet to be analyzed.
The ROMANA 1 and 2 trials were funded by Helsinn Therapeutics.
Temel J, Currow D, Fearon K, et al. Anamorelin for the treatment of cancer anorexia-cachexia in NSCLC: results from the Phase 3 studies ROMANA 1 and 2. Presented at: ESMO Congress 2014: September 26-30, 2014. Abstract 1483O.