# Select cachexia trial patients by the hormone driving their wasting

Source: https://onco.cc/ideas/idea-bio2-gdf15-stratified-enrolment/  
OnCo record `idea-bio2-gdf15-stratified-enrolment` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Wasting has several causes. Measuring the specific hormone in each patient's blood would put the right patients into the right trial instead of mixing everyone together.

## Summary

Cachexia trials have historically enrolled by weight loss criteria alone, mixing inflammatory, anorexic, hypermetabolic and mechanical causes. Plasma GDF-15, interleukin-6, C-reactive protein and resting energy expenditure define mechanistically distinct groups. Enriching for high GDF-15 in anti-GDF-15 trials, and for high interleukin-6 in anti-inflammatory trials, is straightforward and cheap.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Biomarker-stratified enrolment increases the observed treatment effect size in cachexia trials by at least 50% relative to unselected enrolment, converting historically borderline results into clear ones.
- Rationale: Mechanistic stratification rescued many oncology drugs that failed in unselected populations. Cachexia is arguably the least stratified field in oncology despite having measurable, causally relevant plasma markers.
- Proposed test: Retrospectively stratify banked samples from completed cachexia trials by GDF-15 and interleukin-6 and test for treatment-by-biomarker interaction; if present, mandate stratification prospectively.
- Maturity: speculative
- Actor: industry

## Sources

- GDF15: https://en.wikipedia.org/wiki/GDF15

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Proteomics & phosphoproteomics](https://onco.cc/technologies/proteomics/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Cachexia, toxicity and the limits of the patient](https://onco.cc/bottlenecks/b-cachexia-supportive/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- trials: [Ponsegromab phase 2 in cancer cachexia](https://onco.cc/trials/ponsegromab-phase-2/)

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