Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial-level analysis.

ABSTRACT

BACKGROUND: In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. METHODS: After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. RESULTS: Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. CONCLUSIONS: PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.