Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-βRI inhibitor galunisertib.

BACKGROUND: Transforming growth factor beta (TGF-beta) signalling is involved in the development of hepatocellular carcinoma (HCC). We followed changes in biomarkers during treatment of patients with HCC with the TGF-betaRI/ALK5 inhibitor galunisertib. METHODS: This phase 2 study (NCT01246986) enrolled second-line patients with advanced HCC into one of two cohorts of baseline serum alpha-fetoprotein (AFP): Part A (AFP >/=1.5x ULN) or Part B (AFP 20% from baseline) versus non-responders, median OS was 21.5 months versus 6.8 months (p = 0.0015). In TGF-beta1 responders (51% of all patients) versus non-responders, median OS was 11.2 months versus 5.3 months (p = 0.0036). CONCLUSIONS: Consistent with previous findings, both baseline levels and changes from baseline of circulating AFP and TGF-beta1 function as prognostic indicators of survival. Future trials are needed to confirm and extend these results.