Factors Associated with Post-Progression Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib.

Taiga Otsuka,Keisuke Ario,Yuichiro Eguchi,Seiji Kawazoe,Toshihiko Mizuta,Shunya Nakashita,Kimihiko Yanagita,Hiroaki Kawasoe

doi:10.3390/diseases3020068

Abstract

Sorafenib exerts modest antitumor activity in patients with advanced hepatocellular carcinoma (HCC), and radiological progressive disease (rPD) does not always correspond to so-called clinical progressive disease (cPD). We evaluated 101 patients who initiated sorafenib treatment for HCC and assessed post-progression survival (PPS) using the Cox proportional hazards model. PPS was calculated from the date of the first rPD until the date of death or the last follow-up. Using Cox model analysis of the 76 patients who experienced first rPD, we identified the Child-Pugh class, Eastern Cooperative Oncology Group performance status, the best antitumor response during treatment (using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1) and α-fetoprotein levels as independent factors affecting PPS. When these factors were used to define scores ranging from zero to five with a cutoff value of two, PPS of patients who received best supportive care (BSC) after rPD was not statistically significantly different from that of patients who received post-rPD therapy with scores ≥2 (p = 0.220). In contrast, the PPS for the post-rPD therapy group was significantly longer compared with the BSC patients with scores <2 (p < 0.001). Patients who scored ≥2 at their first rPD were judged cPD and as candidates for BSC.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide [1,2]
Seventy-six patients experienced their first radiological progressive disease (rPD), and the remaining 25 patients were either alive without rPD (n = 17) or discontinued sorafenib caused by adverse events before rPD (n = 8)
The present study identifies prognostic factors for post-progression survival (PPS) in patients treated with sorafenib, and we propose a numerical indicator for clinical PD (cPD)

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide [1,2]. The prognosis of HCC depends on its stage at diagnosis. The prognosis is favorable for patients with early. HCC who receive radical therapy, it is poor for those with advanced HCC. Sorafenib is the first targeted agent with significant clinical activity for advanced HCC. Double-blind, randomized phase 3 studies, the SHARP [3] and Asia-Pacific [4] studies, sorafenib provided statistically-significant survival benefits compared with placebo in patients with advanced HCC. Because survival is influenced by second- and beyond-line therapies, reviews of other cancers demonstrate the requirement for post-progression survival (PPS) analysis [5,6,7]

Results

Discussion

Conclusion