Cancer cachexia, also referred to as wasting syndrome, affects patients with multiple forms of cancer. It can lead to weight loss, muscle wasting, and reductions in quality of life, daily functioning, and even survival. There are currently no approved medications for the treatment of cancer cachexia in the United States or Europe, but one new investigational treatment has shown promising results. Ponsegromab, a growth differentiation factor 15 (GDF-15) inhibitor, was studied in a phase II, randomized, double-blind, placebo-controlled trial of 187 patients with cancer cachexia and elevated circulating GDF-15 levels to assess its safety and efficacy and to test the hypothesis that GDF-15 is a main mechanistic driver of cancer cachexia. Patients were randomized to receive ponsegromab at a dose of 100 mg, 200 mg, or 400 mg, or placebo.
At 12 weeks, there was a significant, robust increase in body weight from baseline for all 3 ponsegromab groups as compared with the placebo group, with greater increases at each higher dose level. Furthermore, the effect of 400 mg of ponsegromab was consistent across key subgroups, including cancer time, quartile of serum GDF-15 level, platinum chemotherapy exposure, body mass index, and baseline systemic inflammation. Patients in the 400-mg ponsegromab group also had increased overall activity at 12 weeks compared with the placebo group, with a difference of 72 minutes per day. Adverse events were reported in similar percentages of patients between groups.
High level
The results of this study highlight the potential for ponsegromab as a targeted therapy for treatment of cancer cachexia. Areas for future research include the determination of appropriate timing for ponsegromab initiation in patients with cancer cachexia and the determination of whether ponsegromab-mediated weight gain is related to the magnitude of baseline GDF-15 elevation. The findings also suggest there may be possible implications for other diseases associated with elevated GDF-15 levels and highlight the need for further research into the use of ponsegromab for conditions beyond cancer cachexia.
Ground level
The findings of this study support the hypothesis that GDF-15 is a primary driver of cancer cachexia. This cytokine represents a potential target for further evaluation in clinical trials. If further research leads to the approval of ponsegromab for treatment of cancer cachexia, clinicians may finally have an option to give patients clinically meaningful functional improvement by enabling them to complete important activities of daily living, such as showering, dressing, and light household activities.
