These were clinically meaningful changes in quality of life.
—Jennifer S. Temel, MD
These are incredibly exciting results. The benefits are consistent…. This therapy has the potential to affect cancer therapy across all treatment centers.
—David C. Currow, BMed, MPH, PhD, FRACP
For the first time, studies show that a drug is effective in treating several domains of cancer-related cachexia. Oral anamorelin increased lean body mass, achieved weight gain, and improved quality of life in patients with cancer-related cachexia in two pivotal phase III studies presented together at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid. These studies did not show an effect on hand-grip strength, one of the two coprimary endpoints.
“[These are] the largest randomized controlled [trials] ever conducted in cachexia. Although anamorelin did not improve hand-grip strength, it did improve anorexia/cachexia symptoms and was incredibly well tolerated. Overall survival results are pending and will be presented over time,” said lead author Jennifer S. Temel, MD, Clinical Director of Thoracic Oncology at Massachusetts General Hospital, Associate Director of the Dana-Farber/Partners Cancer Care Hematology/Oncology Fellowship, and Associate Professor at Harvard Medical School, Boston.
“Cachexia is one of the most troubling symptoms of cancer for patients and their families. It can be a limiting factor for treatment of cancer,” said study coauthor David C. Currow, BMed, MPH, PhD, FRACP, Professor of Palliative and Supportive Services at Flinders University, Adelaide, Australia. Dr. Currow spoke about study results at an ESMO press conference.
“For the first time, 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,” he said.
Anamorelin is an investigational agent under development by Helsinn. It is a first-in-class oral ghrelin receptor agonist. Release of ghrelin stimulates multiple pathways that regulate body weight, lean body mass, appetite, and metabolism.
Patients with cancer-related cachexia keep losing weight and often have poor appetite. They are often too sick to get the cancer treatment that they need. A drug such as anamorelin may allow patients to be well enough to continue with their cancer treatment.
Identically Designed Trials
ROMANA 1 (N = 484) and ROMANA 2 (N = 495) were identically designed phase III studies that randomly assigned patients with inoperable stage III and IV non–small lung cancer (NSCLC) and cachexia in a 2:1 ratio to receive either anamorelin at 100 mg/d or placebo for 12 weeks. Eligible patients were to have a life expectancy of greater than 4 months. The majority of patients were receiving chemotherapy, and approximately 12% were getting radiotherapy. Cachexia was defined as ≥ 5% weight loss within the past 6 months or body mass index < 20 kg/m2.
After 12 weeks, patients had the option of blinded continuation on the same arm to which they were originally randomized, continuing anamorelin or placebo, and results of this study (ROMANA 3) will be presented in the future.
Both studies found that patients randomly assigned to placebo continued to lose weight and lean body mass over the 12-week study period, while those assigned to anamorelin gained lean body mass. The differences between the two groups for weight were highly significant at weeks 3, 6, 9, and 12. (P < .0001 for all comparisons).
In ROMANA 1, median increase in lean body mass was 1.10 kg with anamorelin vs a loss of 0.44 kg in the placebo group. In ROMANA 2, median increase was 0.75 kg compared with a loss of 0.96 kg on placebo (P < .0001 for both studies). The net effect of difference was more than 1.5 kg in both studies at 12 weeks.
In ROMANA 1, body weight increased by an average of 2.2 kg on anamorelin vs 0.14 kg on placebo. In ROMANA 2, body weight increased by an average of 0.95 kg vs a loss of 0.57 kg on placebo (P < .0001 for both studies).
Both groups declined in hand-grip strength over the course of the study.
Further, quality of life as assessed by the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) Anorexia-Cachexia Domain, also showed a significant difference between the two treatment arms at all time points favoring anamorelin treatment over placebo, especially for ROMANA 1. This instrument included questions about appetite and appearance.
“These were clinically meaningful changes in quality of life,” Dr. Temel noted.
Low rates of toxicity were seen. The most common adverse events were nausea and hyperglycemia. A few patients had diabetes, she said.
Hyperglycemia is expected as part of the mechanism of action, and events were well managed using standard clinical protocols. “These effects were specifically sought given the effect of ghrelin (and therefore ghrelin agonists) on glucose metabolism,” Dr. Currow explained to The ASCO Post.
“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,” Dr. Currow said.
Patients will be followed for survival for 1 year from trial entry. ■
Disclosure: Drs. Temel and Currow reported no potential conflicts of interest. For full disclosures of the study authors, visit www.esmo.org/Conferences/ESMO-2014-Congress/Abstracts.
1. 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. ESMO 2014 Congress. Abstract
1483O-PR. Presented September 27, 2014.
The study was well performed and was a good representative sample of patients with cachexia,” said formal discussant Florian Scotté, MD, PhD, a medical oncologist in the Department of Oncology at the Georges Pompidou European Hospital, Paris, regarding the study presented by Temel et al at the ESMO ...