# Treat cachexia before it starts

Source: https://onco.cc/ideas/idea-cachexia-gdf15-prevention/  
OnCo record `idea-cachexia-gdf15-prevention` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cachexia, the muscle wasting driven partly by the hormone GDF-15, kills cancer patients and stops chemotherapy being completed, and late muscle loss is largely irreversible. Ponsegromab, an anti-GDF-15 antibody, reversed weight loss in established cachexia in 2024; the next test is a phase 3 giving it from first-line chemotherapy in pancreatic cancer to prevent wasting rather than treat it.

## Summary

This idea proposes treating cachexia before it starts: wasting is a common cause of death in cancer and makes treatment impossible, and now that an effective anti-cachexia drug is in phase 3, the question is whether starting early prevents it. Ponsegromab reversed weight loss in established cachexia (2024), and GDF-15 rises early in pancreatic and lung cancer, so prevention could improve chemotherapy tolerance (Cancer cachexia pathway). The hypothesis is that anti-GDF-15 therapy from diagnosis in high-GDF-15 patients preserves muscle and increases chemotherapy completion and survival, because late muscle loss is largely irreversible. The test is a randomised phase 3 of ponsegromab from first-line chemotherapy in Pancreatic ductal adenocarcinoma; Non-small-cell lung cancer and Gastric cancer are also in scope.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: mechanism; open-question
- Hypothesis: Anti-GDF-15 therapy started at diagnosis in high-GDF-15 patients preserves muscle mass and increases chemotherapy completion and overall survival.
- Rationale: Muscle loss is largely irreversible late; GDF-15 is measurable and causal; ponsegromab is safe.
- Proposed test: Randomised phase 3 of ponsegromab vs placebo from first-line chemotherapy in metastatic pancreatic cancer with elevated GDF-15, endpoints OS and relative dose intensity.
- Maturity: early-clinical

## Sources

- Groarke et al., Ponsegromab for the treatment of cancer cachexia (NEJM 2024): https://doi.org/10.1056/NEJMoa2409515

## Connected records

- cancers: [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Exercise & lifestyle oncology](https://onco.cc/technologies/exercise-oncology/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/), [Fred Hutchinson Cancer Center](https://onco.cc/institutions/fred-hutch/)
- pathways: [Cancer cachexia](https://onco.cc/pathways/cachexia-biology/), [JAK-STAT signalling](https://onco.cc/pathways/jak-stat/)
- trials: [Ponsegromab phase 2 in cancer cachexia](https://onco.cc/trials/ponsegromab-phase-2/)
- roadmaps: [Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment](https://onco.cc/roadmaps/nutrition-lifestyle-roadmap/)

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