Nourishing Strength: A New Chapter in Cancer Supportive Care

Thanks to remarkable advances in supportive medications—like antiemetics for chemotherapy, growth factors, and biologic agents—many cancer patients now tolerate treatments more comfortably than ever before. Studies have shown that effective supportive strategies reduce treatment interruptions, improve dose intensity, and ultimately enhance survival outcomes. For instance, the widespread use of G-CSF has significantly lowered febrile neutropenia rates, allowing more patients to receive full-dose chemotherapy on schedule.

One of the most challenging side effects in cancer care is cachexia — a complex syndrome of involuntary weight loss, poor appetite, muscle wasting, and fatigue. It is distinct from simple malnutrition and is driven by inflammation and metabolic changes related to the cancer itself. Cachexia affects a large proportion of patients with advanced cancers, including but not limited to Stage IV non–small-cell lung cancer (NSCLC), and is associated with reduced quality of life, diminished treatment tolerance, and worse survival outcomes.

As we continue to expand our arsenal of supportive therapies, a new contender has emerged from one of the latest issues of the New England Journal of Medicine: a GDF-15 inhibitor showing promise in treating cancer cachexia.

Specifically, GDF-15 is a natural signal in the body that, when present in high amounts during cancer, can tell the brain to reduce appetite and cause the body to burn muscle and fat. Ponsegromab works by blocking this signal, helping people feel hungrier, keep their strength, and maintain a healthier weight.

GDF-15 Inhibition: A Potential Breakthrough for Cachexia

In a randomized Phase II trial of 187 patients with elevated GDF-15 levels and cancer cachexia (including ~40% with NSCLC), the monoclonal antibody ponsegromab was administered subcutaneously (100, 200, or 400 mg every 4 weeks for three doses). Compared to placebo, the treatment led to:

• Weight gains at 12 weeks: +1.22 kg (100 mg), +1.92 kg (200 mg), and +2.81 kg (400 mg).
• Improved appetite and reduced cachexia symptoms, especially at the highest dose.
• Increased physical activity: the 400 mg group showed significant daily activity gains (more than 1 additional hour out of bed or in a chair) versus placebo.

Importantly, ponsegromab was well tolerated—with fewer adverse events than placebo—and did not seem to interfere with ongoing cancer treatments.

These findings are groundbreaking because they validate GDF-15 not just as a marker but as a driver of cachexia, and offer a potential therapeutic approach for a condition that currently lacks effective treatments.

Looking Ahead: Expanding the Reach of GDF-15 Blockade

Commentaries accompanying the NEJM article further explore the broader implications of GDF-15 inhibition—not only for cancer cachexia but also for other conditions in which GDF-15 is elevated, such as chronic kidney disease and geriatric failure-to-thrive syndromes.

With regulatory steps in motion, Pfizer is planning larger, registration-enabling trials in 2025. If successful, this could pave the way for the first ever FDA-approved therapy for cancer cachexia—and a major advancement in supportive oncology.

References

• Groarke JD, Crawford J, Collins SM, et al. Ponsegromab for the treatment of cancer cachexia. N Engl J Med. 2024;391(24):2291-2303. doi:10.1056/NEJMoa2409515 (pfizer.com, pubmed.ncbi.nlm.nih.gov)
• “Will Ponsegromab Be a Game Changer for Cancer Cachexia?” Cancer Currents Blog, NCI, Oct 17, 2024 (cancer.gov)
• Pfizer press release: Pfizer presents positive data from Phase II study of ponsegromab in patients with cancer cachexia. Sept 14, 2024 (pfizer.com)
• Fabbricatore R. Ponsegromab reduces symptoms linked to cancer cachexia, elevated GDF-15. CancerNetwork, Jan 15, 2025 (cancernetwork.com)
• Melero I. GDF-15 blockade: A multi-directional approach to … PMC, 2025 (pmc.ncbi.nlm.nih.gov)