Insulin-Like Growth Factor Axis and Survival in Metastatic Hormone-Sensitive Prostate Cancer: Post-Hoc Analysis From the ENZAMET Phase 3 Trial.

Abstract

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. 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. 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%). 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.