Written by Peter Liu
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Ponsegromab, a monoclonal antibody that inhibits differentiation factor 15 (GDF-15), caused more weight gain, less cachexia, and increased physical activity in patients with cancer cachexia.
Ponsegromab inhibits GDF-15 to treat cancer cachexia
Until recently, safe and effective medications to treat cancer cachexia have been limited. This phase 2, randomized, double-blind trial investigated the efficacy and safety of ponsegromab in patients with cancer cachexia. 187 patients were assigned to receive ponsegromab (100 mg, 200 mg, 400 mg) or placebo every four weeks for 12 weeks. Ponsegromab groups achieved significant weight gain compared to placebo of 2.69–6.19 lbs. Appetite and physical activity only improved in the 400-mg group.
This study was limited to patients with colorectal, non-small-cell lung, and pancreatic cancer, and it is unclear if similar results could be reproduced with other cancers. While adverse event rates were similar among all study arms, the ponsegromab arms had higher mortality rates and serious adverse event rates than placebo arm. None of these events were clearly linked with ponsegromab, but this warrants further scrutiny as we gain more experience with this medication. Additionally, it would make sense to compare ponsegromab to low-dose olanzapine for patients with new advanced gastric, hepatopancreaticobiliary, or lung cancer planning to undergo chemotherapy, as olanzapine helped patients gain weight (difference of 11 lbs compared to placebo), improved quality of life scores, and reduced chemotherapy toxicity. While the patient populations differed (70% of patients in the olanzapine trial did not have severe malnutrition), the similarity of these two studies suggest that both may be reasonable options for cancer-related malnutrition.
How does this change my practice?
In my inpatient practice, olanzapine will likely remain a lower-cost and more readily available treatment for cancer-related cachexia and will persist as my first-line medication for this indication. However, it is helpful to know that there will likely be another available drug that is a monthly subcutaneous option which targets a specific mechanism of cancer cachexia.
Source
Ponsegromab for the Treatment of Cancer Cachexia. N Engl J Med. 2024 Dec 19;391(24):2291-2303. doi: 10.1056/NEJMoa2409515. Epub 2024 Sep 14. PMID: 39282907
