Cancer cachexia, a severe wasting syndrome often experienced by patients with advanced cancer, leads to substantial weight loss, muscle wasting, and a reduced quality of life. To date, there are no effective treatments for cancer cachexia in Europe or the United States, leaving a significant gap in supportive care for these patients. However, a new study on ponsegromab, a humanised monoclonal antibody that inhibits the growth differentiation factor 15 (GDF-15), has shown promise in addressing this unmet need.

Monoclonal antibodies are laboratory-made proteins designed to bind to specific targets in the body, such as proteins on the surface of cancer cells or, in this case, a cytokine involved in cachexia. By blocking these targets, monoclonal antibodies can modulate disease processes and improve patient outcomes.

In a recent international, double-blind trial involving 187 patients with various advanced cancers (including non–small-cell lung, pancreatic, and colorectal cancers) and elevated levels of GFD-15, ponsegromab demonstrated significant benefits in managing cachexia symptoms. Patients were randomly assigned to receive either placebo or ponsegromab in doses of 100 mg, 200 mg, or 400 mg, administered subcutaneously every four weeks. After 12 weeks, patients who received the 400 mg dose of ponsegromab showed substantial weight gain, averaging a 2.81 kg increase, along with improved appetite, physical activity, and overall quality of life compared to the placebo group.

The study’s results highlight the role of GDF-15 in cancer cachexia and confirm it as a promising therapeutic target. Ponsegromab not only increased body weight but also reduced the severity of cachexia symptoms, suggesting a potential role for this treatment in improving the daily lives of patients with advanced cancer. Side effects in the ponsegromab groups were generally mild to moderate, with similar rates of adverse events between the ponsegromab and placebo groups.

This trial underscores ponsegromab’s potential as the first effective targeted treatment for cancer cachexia, opening new possibilities for supportive care in patients with advanced digestive and other cancers. Further studies will be essential to confirm these benefits in broader patient populations, but ponsegromab may represent a new frontier in improving the quality of life for cancer patients experiencing cachexia.

The results of this study are published in the New England Journal of Medicines

Author:
Marianna Vitaloni