Serum α-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma

Abstract

Background. The role of serum ␣-fetoprotein (AFP) as a marker for treatment response in patients with hepatocellular carcinoma (HCC) receiving systemic therapy is poorly defined.Methods. A retrospective study was performed on patients with advanced HCC enrolled in five phase II clinical trials. Serum AFP was prospectively collected at baseline and at different time points through treatment in parallel with radiologic response and clinical outcome. Patients were separated into three groups based on a 50% change in serum AFP from baseline. Overall survival (OS), progression-free survival (PFS), and radiologic responses were compared between groups using log-rank and Wilcoxon tests.Results. Of 144 patients, 107 met the eligibility criteria. Eighteen patients experienced a >50% AFP decline, 57 patients had a >50% AFP increase, and 32 patients had a

The Significance of Early Alpha-Fetoprotein Level Changes in Predicting Clinical and Survival Benefits in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib

“…There is an absence of published data in the literature regarding the trend of AFP changes in patients receiving targeted therapy treatment for advanced HCC [6]. Llovet et al reported the baseline level of AFP as one of the prognostic indicators for survival in Sorafenib HCC Assessment Randomized Protocol (SHARP) [2] trial; however, the serial AFP response to sorafenib was not provided.…”

“…Similarly, in Asian sorafenib trials [3], the serial change of AFP during sorafenib treatment was not measured either. Despite the established role of using AFP in screening, diagnosis, and surveillance of HCC, its use as a surrogate marker for treatment response remains controversial [6]. More recently, there is renewed interest in exploring the role of serial AFP changes as a serological surrogate for treatment response in HCC patients receiving systemic treatment.…”

“…Chan et al [8] reported that a 20% decrease in serum AFP was strongly associated with radiological response and overall survival benefit in advanced HCC patients receiving systemic chemotherapy. Similarly, a retrospective analysis by Vora et al [6] suggested that Ͼ50% AFP decrease from the baseline during treatment may serve as a useful surrogate marker for clinical outcome in patients with advanced HCC receiving systemic therapy. Interestingly, in this analysis, patients were recruited from five different clinical trials: two chemotherapy trials, one thalidomide trial, and two targeted therapy trials.…”

“…However, most advanced HCC patients have underlying cirrhosis; in the background of cirrhosis, accurate radiological assessment of the liver lesions is difficult because of the underlying fibrosis and the presence of regeneration nodules [6,7]. Importantly, in the era of targeted therapy, most of the targeted agents like sorafenib are rather cytostatic than cytotoxic.…”

Drug Therapy: Sorafenib

“…Although AFP as an endpoint was not well studied in the sorafenib trials, it may provide additional insight into the clinical activity in any one patient. 26 The success in keeping patients on therapy requires proactive management of side effects by the treating physician. Patients should be assessed within 7-10 days of starting drug for adverse events.…”