Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC.
IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430). IL4, IL6, and GDF15 levels were measured by ELISA. Monocytes and dendritic cells were treated with 10% plasma from men with high or low GDF15 or recombinant GDF15.
IntVal: Higher GDF15 levels at BL and Day 21 were associated with shorter overall survival (OS) (BL; p = 0.03 and Day 21; p = 0.004). IL4 and IL6 were not associated with outcomes. ExtVal: Higher GDF15 levels at BL and Day 42 predicted shorter OS (BL; p < 0.0001 and Day 42; p < 0.0001). Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes (p = 0.03), but was not replicated by recombinant GDF15.
Elevated circulating GDF15 is associated with poor prognosis in men with mCRPC receiving docetaxel and may be a marker of changes in the innate immune system in response to docetaxel resistance. These findings provide a strong rationale to consider GDF15 as a biomarker to guide a therapeutic trial of drugs targeting the innate immune system in combination with docetaxel in mCRPC.
The Prostate. 2024 Mar 27 [Epub ahead of print]
Kate L Mahon, Sarah Im Sutherland, Hui Ming Lin, Martin R Stockler, Howard Gurney, Girish Mallesara, Karen Briscoe, Gavin Marx, Celestia S Higano, Johann S de Bono, Kim N Chi, Georgina Clark, Samuel N Breit, David A Brown, Lisa G Horvath
Chris O'Brien Lifehouse, Sydney, New South Wales, Australia., Prostate Cancer Research Group, Garvan Institute of Medical Research, Sydney, New South Wales, Australia., Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia., Medical Oncology Department, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales, Australia., Northern Haematology Oncology Group, Sydney, New South Wales, Australia., BC Cancer Agency, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Royal Marsden Hospital and Institute of Cancer Research, London, UK., St Vincent's Centre for Applied Medical Research, Sydney, New South Wales, Australia., School of Clinical Medicine, University of NSW, Sydney, New South Wales, Australia.