GDF-15 is Upregulated in Patients that Develop Cachexia during Chemoradiotherapy for Head and Neck Cancer
| Thursday, August 14, 2025 |
| 10:45 AM - 10:52 AM |
| Ballroom 2 and 3 |
Overview
Prof Joanne Bowen
Speaker
Prof Joanne Bowen
Professor, Physiology
University Of Adelaide
GDF-15 is Upregulated in Patients that Develop Cachexia during Chemoradiotherapy for Head and Neck Cancer
Abstract
Background:
Cachexia is a challenging complication of cancer and its treatment, associated with an increased risk of death. Growth differentiation factor 15 (GDF15) is a known driver of cachexia, with ponsegromab (GDF15 mAb) showing therapeutic success in a Phase II trial conducted in people with lung, pancreatic and colorectal cancer. The role of GDF15 in cachexia aetiology in other cancer types is unknown.
As such, the objective of this study was to quantify circulating GDF15 in people with head and neck cancer (HNC) and determine the relationship with indicators of cachexia.
Methods:
Adults diagnosed with HNC, scheduled to receive definitive cisplatin-based chemoradiotherapy, were recruited from four tertiary hospitals in Australia and Italy. Cachexia was determined using a variety of clinical parameters, including weight, grip strength, and upper arm circumference (UAC), each assessed at baseline, week 3 and end of treatment. GDF15 was quantified in serially-collected serum using a commercial ELISA.
Results:
To date, N=38 have been recruited; the results presented in this abstract relate to the N=19 participants recruited from Australia. These participants were predominantly male (79%) with a mean age of 65+/-4 years. 95.7% (18/19) participants met the diagnostic criteria for cachexia, with an average weight loss of 11% over the course of treatment. This was accompanied by a 12% and 12.6% average reduction in grip strength and UAC respectively. Serum GDF15 levels were highly elevated following chemoradiotherapy compared to baseline (4.5 Fold, P<0.0001), and correlated with reductions in weight (R²=0.2, P=0.0027), UAC (R²=0.1714, P=0.0047) and grip strength (R²=0.3779, P<0.0001).
Conclusions:
These pilot data suggest aberrant GDF15 production occurs in HNC patients during chemoradiotherapy, identifying a new clinical cohort that may benefit from ponsegromab.
Cachexia is a challenging complication of cancer and its treatment, associated with an increased risk of death. Growth differentiation factor 15 (GDF15) is a known driver of cachexia, with ponsegromab (GDF15 mAb) showing therapeutic success in a Phase II trial conducted in people with lung, pancreatic and colorectal cancer. The role of GDF15 in cachexia aetiology in other cancer types is unknown.
As such, the objective of this study was to quantify circulating GDF15 in people with head and neck cancer (HNC) and determine the relationship with indicators of cachexia.
Methods:
Adults diagnosed with HNC, scheduled to receive definitive cisplatin-based chemoradiotherapy, were recruited from four tertiary hospitals in Australia and Italy. Cachexia was determined using a variety of clinical parameters, including weight, grip strength, and upper arm circumference (UAC), each assessed at baseline, week 3 and end of treatment. GDF15 was quantified in serially-collected serum using a commercial ELISA.
Results:
To date, N=38 have been recruited; the results presented in this abstract relate to the N=19 participants recruited from Australia. These participants were predominantly male (79%) with a mean age of 65+/-4 years. 95.7% (18/19) participants met the diagnostic criteria for cachexia, with an average weight loss of 11% over the course of treatment. This was accompanied by a 12% and 12.6% average reduction in grip strength and UAC respectively. Serum GDF15 levels were highly elevated following chemoradiotherapy compared to baseline (4.5 Fold, P<0.0001), and correlated with reductions in weight (R²=0.2, P=0.0027), UAC (R²=0.1714, P=0.0047) and grip strength (R²=0.3779, P<0.0001).
Conclusions:
These pilot data suggest aberrant GDF15 production occurs in HNC patients during chemoradiotherapy, identifying a new clinical cohort that may benefit from ponsegromab.
Biography
Prof Bowen is Head of the Cancer Treatment & Toxicities Group in the School of Biomedicine, University of Adelaide. Her group focusses on prediction, prevention and management of complications of therapy. She has a special interest in the role of the microbiome in modulating risk of severe gastrointestinal and neurological toxicities. She has worked extensively with industry partners to develop novel methods to better understand and treat common side effects of chemotherapy and targeted therapies. Prof Bowen is a current executive member of the Multinational Association of Supportive Care in Cancer.
Session Chair
Tim Clay
St John Of God Subiaco Hospital
