Early PIVKA-II Response Associated with Treatment Efficacy and Survival Outcomes for Patients with Advanced Hepatocellular Carcinoma Receiving Immune Checkpoint Inhibitors and Targeted Therapy.

Background & aims: Prothrombin induced by vitamin K absence-II (PIVKA-II) levels have been reported to correlate with hepatocellular carcinoma (HCC) prognosis, but its utility for assessing early treatment response remains underexplored. This study evaluated early PIVKA-II changes for predicting response and survival in HCC patients undergoing immune checkpoint inhibitors (ICIs) and targeted therapy.

Methods: Eighty-two HCC patients were enrolled. Serum PIVKA-II levels were measured at baseline and after the first treatment cycle. Patients were stratified based on early PIVKA-II dynamics into a biochemical response group (≥50% reduction, n=40) and a non-response group (<50% reduction, n=42). Logistic regression and Cox proportional hazards models were used to identify predictors of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results: Time-dependent ROC analysis established ≥50% PIVKA-II decline as the early response threshold. The PIVKA-II response group had a significantly higher proportion of patients with Child-Pugh A, a lower incidence of extrahepatic metastasis, and significantly higher ORR (82.5% vs 38.1%, P<0.001). Median PFS and OS were not reached in the PIVKA-II responder group, compared to 8.9 months and 16.7 months, respectively, in the non-responder group (both P < 0.001). Multivariate analysis confirmed early PIVKA-II response as an independent predictor of PFS (HR=0.687, P<0.001) and OS (HR=0.709, P<0.001). Notably, in AFP-negative patients, an early PIVKA-II response was predictive of ORR and was associated with significantly longer PFS and OS.

Conclusion: Early PIVKA-II response effectively predicts treatment response and prognosis in advanced HCC patients receiving ICI and targeted therapy, especially in AFP-negative patients.