Cancer-related cachexia is a debilitating condition that has had no effective treatment thus far. Its symptoms include loss of lean body mass, as well as muscle wasting and loss of appetite.
A pair of pivotal international phase 3 studies suggest that the investigational oral drug anamorelin hydrochloride can increase lean body mass, achieve weight gain, and improve quality of life (QOL). This drug is the first to hold promise for improving all of these aspects of cancer-related cachexia.
“Cachexia is one of the most troubling symptoms of cancer for patients and their families. This is a very exciting study. For the first time in more than a decade, a drug is effective in treating cachexia. This will significantly change how we think about cancer-related cachexia and how we treat patients with cancer,” said study coauthor David Currow, MD, of Flinders University in Adelaide, Australia.
Treatment with anamorelin may enable patients to continue with their cancer treatment, he said. Currow discussed these results at a press conference during the 2014 Congress of the European Society for Medical Oncology.
Jennifer Temel, MD, of the Dana Farber Cancer Institute in Boston, MA, presented the results in an oral session at the congress. “Cancer-related cachexia anorexia causes progressive functional impairment, inactivity, and can negatively impact prognosis. Current treatment options have limited efficacy and potential risks, especially in patients with cachexia,” Temel told listeners.
Anamorelin is a first-in-class, orally administered ghrelin receptor agonist. Release of ghrelin stimulates multiple pathways that regulate body weight, lean body mass, appetite, and metabolism.
ROMANA 1 (N = 484) and ROMANA 2 (N = 495) were identically designed phase 3 studies, representing the largest phase 3 trials conducted to date to assess the safety and efficacy of anamorelin in patients with cachexia. Patients with stage III or IV unresectable non–small-cell lung cancer and cancer-related cachexia were randomized 2:1 to receive either anamorelin or placebo for 12 weeks. All patients enrolled in the trials had a life expectancy of >4 months.
For study purposes, cachexia was defined as ≥5% weight loss within the past 6 months or a body mass index <20 kg/m2. At the end of 12 weeks, patients had the option to continue on anamorelin for an additional 12 weeks, and those results (ROMANA 3) will be presented at a later date.
Temel noted that the studies had broad inclusion criteria. Patients could be on chemotherapy, maintenance chemotherapy, or no chemotherapy.
In both ROMANA 1 and ROMANA 2, patients randomized to placebo continued to lose weight and lean body mass over the 12-week study period, whereas those randomized to anamorelin gained weight and lean body mass. The difference between the 2 groups for lean body mass and body weight increases was highly significant in both trials (P < .0001 for all comparisons).
The study failed to show an improvement in handgrip strength, which was a coprimary end point.
QOL (a secondary end point) was assessed, in part, by the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire, which looks at patient symptoms and concerns related to anorexia-cachexia, including appetite, early satiety, and general health. In both trials, a significant difference was observed between the 2 treatment arms on the FAACT anorexia/cachexia domain at all time points, favoring anamorelin treatment over placebo. Results for QOL in this domain were slightly more robust for ROMANA 1 (P = .0012) than for ROMANA 2 (P = .0150). Patients were followed for 1 year for survival.
Rates of toxicity related to anamorelin were low. The most common adverse events included nausea, hyperglycemia, and a few cases of diabetes.
“These are incredibly exciting results. The benefits are consistent. Up until now you couldn’t change lean body mass in patients with cancer-related cachexia. This therapy has the potential to affect cancer therapy across all treatment centers,” Currow said.
The formal discussant of this trial, Florian Scotté, MD, of Georges Pompidou European Hospital in Paris, France, commended the authors on a well-designed study for a condition with few good treatment options.
He pointed out that other studies of new agents have had disappointing results. “I look forward to hearing the long-term follow-up on these patients. This is a difficult problem, and we have to pay full attention to this, working with a multidisciplinary approach,” Scotté said. n
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: 2014 Congress of the European Society for Medical Oncology; September 26-30, 2014; Madrid, Spain. Abstract 1483O_PR.