Rapid Fire Best of the Best Oral 2025 Joint Meeting of the COSA ASM and IPOS Congress

GDF-15 levels and clinical correlates in head and neck cancer patients: developing a risk model for cachexia (125902)

Connor Williams 1 2 , Claire Vieyra 1 , Caelleb Morcom 1 2 , Pierluigi Bonomo 3 , Almalina Bacigalupo 4 , Maria Teriaca 5 , Laura Bonavita 5 , Joanne Bowen 6 , Egidio Del Fabbro 7 , Tateaki Naito 8 , Tomoya Yokota 9 , Paolo Bossi 10 , Hien Le 11 12 , Hannah Wardill 1 2
  1. The University of Adelaide, Adelaide, SA, Australia
  2. Precision Medicine (Cancer) Theme, Supportive Oncology Research Group, The South Australian Health and Medical Research Group, Adelaide, South Australia
  3. Radiation Oncology , Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
  4. Radiation Oncology Department, IRCCS Ospedale Policlinco San Martino, Genoa, Italy
  5. IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
  6. The School of Biomedicine , The University of Adelaide, Adelaide, South Australia
  7. Palliative Care , Medical College of Georgia, Augusta University, Augusta, Georgia, USA
  8. Division of Thoracic Oncology, Shizuoka Cancer Centre, Shizuoka, Japan
  9. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
  10. Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Milan, , Italy
  11. Department of Radiation Oncology, Central Adelaide Local Health Network, Adelaide, Australia
  12. Allied Health and Human Performance, University of South Australia, Adelaide, South Australia

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. The objective of this study is 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: The results presented in this abstract relate to the N=41 participants recruited from Australia and Milan (Italy). These participants were predominantly male (79%) with a mean age of 65+/-8 years. 87.8% (36/41) participants met the diagnostic criteria for cachexia, with an average weight loss of 9.04% over the course of treatment. This was accompanied by 12% and 12.6% average reductions in grip strength and UAC respectively. Weight loss persisted 3 months beyond treatment end, with an average loss of 10.47% compared to pre-treatment weight. Notably, 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, identifying a new clinical cohort that may benefit from ponsegromab.