Insulin-Like Growth Factor Axis and Survival in Metastatic Hormone-Sensitive Prostate Cancer: Post-Hoc Analysis From the ENZAMET Phase 3 Trial
In brief
A higher IGF-1-to-binding-protein ratio tracked with 25% lower mortality in prostate cancer
In a post-hoc analysis of 845 men with metastatic hormone-sensitive prostate cancer, those with higher baseline IGF-1 relative to its binding protein had a 25% lower risk of death and an 18% lower risk of clinical progression than those with the lowest ratio. The ratio was linked to prognosis, not greater benefit from enzalutamide or docetaxel.
- Journal
- The Prostate (Q1)
- Published
- 27 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Michael A Cilento, Hui-Ming Lin, Nicole Yeung, Rachel M N Kim, Neil Portman, Martin R Stockler, et al.
- PMID
- 42801727
- DOI
- 10.1002/pros.70245
Why clinicians should know about it
- Picked for Urology (paper of the day, 29 September 2026): IGF-1:IGFBP1 ratio and survival in mHSPC
Abstract
BACKGROUND: A higher ratio of IGF-1:IGF binding protein 1 (IGFBP1) was associated with improved prognosis in the CHAARTED trial of docetaxel in participants with metastatic hormone-sensitive prostate cancer (mHSPC). The ENZAMET trial demonstrated the survival benefit of adding enzalutamide to androgen deprivation therapy (ADT) in mHSPC, and included participants who also received docetaxel as standard of care. The aim of this study was to validate the association between levels of circulating IGF-1 and IGFBP1 and survival of ENZAMET participants. METHODS: IGF-1 and IGFBP1 levels were measured in baseline plasma from 845 ENZAMET participants, and associations with clinical progression-free survival (cPFS) and overall survival (OS) were assessed as a post-hoc analysis. RESULTS: A high baseline plasma ratio of IGF-1:IGFBP1 (upper two tertiles) was associated with improved OS (HR 0.75, p 0.008) and improved cPFS (HR 0.82, p 0.034) compared to the lowest tertile. IGF-1:IGFBP1 was not predictive of enzalutamide or docetaxel benefit (no significant interaction with treatment arm or docetaxel use). In participants in the enzalutamide arm, IGF-1:IGFBP1 was an independent predictor for OS and cPFS in bivariable analysis with docetaxel use. The rate of high volume disease was similar in patients with lower IGF-1:IGFBP1 ratio and those with high ratio (~50%). CONCLUSIONS: This analysis demonstrated a consistent association of improved prognosis with high IGF-1:IGFBP1 in mHSPC, but did not identify which participants benefited from docetaxel when treated with enzalutamide.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.