Cachexia is a condition that causes weight, muscle and fat loss, as well as physical weakness, in people with cancer. To date, there are no Food and Drug Administration-approved medications to prevent or treat cachexia, making it an urgent, unmet need in cancer research and treatment.
New clinical trial results published in The New England Journal of Medicine suggest a promising new therapy could help. The Pfizer-sponsored study enrolled 187 participants across the world — including 10 from Oregon Health & Science University, the most of any clinical trial site in North America — in a study to better understand if the therapy ponsegromab could help participants increase body weight and appetite, and help with other cachexia symptoms.
"This monthly subcutaneous injection improved weight, appetite and quality of life in ways I have not seen," says medical oncologist Eric Roeland, M.D., FASCO, FAAHPM, an associate professor of medicine (hematology and medical oncology and palliative care) in the OHSU School of Medicine. "Suddenly, people were gaining weight, they were hungry, and they were enjoying food. That's not something you typically hear from people living with advanced cancer and receiving cancer therapy. Food is usually a huge struggle. This study marks a major step forward in this field."
The participants in the phase II randomized controlled study were undergoing treatment for one of three types of cancer — lung, colorectal or pancreatic cancer. Participants were given a once-monthly injection of ponsegromab, a monoclonal antibody that stimulates the immune system, and the resulting data were clear: The treatment demonstrated improved weight gain — 6.6 pounds in the highest-dose group — compared with those who received the placebo over 12 weeks. Study participants who received ponsegromab also reported improvement in appetite and cachexia symptoms, overall physical activity and skeletal muscle mass.
Stimulating the appetite
Ponsegromab is a monoclonal antibody, meaning a lab-manufactured clone of the body's antibodies, designed to stimulate the body's immune system. Ponsegromab was made to target a hormone and protein often elevated in people with cancer called growth differentiation factor 15, or GDF-15.
This clinical trial demonstrated that GDF-15 inhibition with ponsegromab improved body weight, symptoms and overall activity in patients with cancer cachexia and elevated GDF-15, supporting the idea of its role as a driver of cachexia.
Roeland adds it is notable that this treatment had no safety issues with participants: "All of our cancer treatment therapies have some side effects. But we haven't seen any concerns with this study so far."
"I knew we were onto something when the patients, caregivers, referring oncology clinicians were eager to get their patients on this study," he says.
'Haven't had anything like this'
While sometimes associated with certain types of cancer, Roeland says cachexia can occur in up to 80% of people with advanced cancer, depending on the cancer type.
"The weight loss, appetite loss and fatigue are all connected to cachexia; it's not something the patient can control," he says. "There's a key difference between cachexia and general weight loss — cachexia is driven by cancer and treatment. It means people are burning calories in a way you normally wouldn't."
On top of that, Roeland says hormonal changes that occur during cancer treatment can further a patient's decreased appetite.
"It makes it even more challenging because even looking at food or smelling food can make it very challenging to eat for patients living with cancer," he says.
Because appetite has been a persistent issue for people with cachexia, Roeland, who is also the lead author on cancer cachexia guidelines for the American Society of Clinical Oncology, says it makes him optimistic about this study's positive findings.
"I've been involved in studies in this space for more than 15 years, and honestly, we haven't had anything like this in the field of cancer cachexia."
Additional late-stage clinical trials will be conducted before seeking FDA approval.
Improving quality of life
The new study is one example of several "symptom science" clinical trials underway at OHSU, including a different open clinical trial for patients with cachexia at OHSU.
Roeland joined the OHSU Knight Cancer Institute with the mission of developing a research program focused on minimizing treatment-related toxicity and improving the quality of life of people living with cancer. The Symptom Science team includes researchers in the basic biology of cancer, oncology, nursing, palliative care, exercise and nutrition.
Learn more about OHSU's Symptom Science program, a clinical research program focused on minimizing treatment-related toxicity and improving the quality of life of people with cancer.
Roeland says it's important to acknowledge the patients and their caregivers who participated in this clinical trial, as well as their referring oncologists and clinical teams.
"This trial's success depended on referrals from the thoracic oncology, gastrointestinal oncology and Community Hematology-Oncology teams," he says. "We are also incredibly grateful to the OHSU Knight Cancer Institute for supporting this program to optimally care for patients as people living with cancer."
