Clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment

Abstract

Aim This study aimed to investigate the clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods Of 122 patients, 103 were radiologically confirmed as progressive disease (PD) (sorafenib‐refractory group), and 19 discontinued sorafenib therapy due to adverse events prior to radiologic PD (sorafenib‐intolerant group). Patients in the sorafenib‐refractory group were divided into two subgroups each, according to their eligibility for second‐line treatment (second‐line‐in and ‐out group), regorafenib (RESORCE‐in and ‐out group), or ramucirumab (REACH‐2‐in and ‐out group). Results Patients included in the non‐candidate group were those with α‐fetoprotein level <400 ng/mL (n = 51, 49.5%), daily sorafenib dose <400 mg (n = 44, 42.7%), Child–Pugh B or C (n = 40, 38.8%), and Eastern Cooperative Oncology Group performance status score ≥2 (n = 24, 23.3%). The percentages of candidates were 57.3% for second‐line, 35.0% for regorafenib, and 23.3% for ramucirumab. The median post‐progression survival (PPS) was significantly longer for the second‐line‐in and the RESORCE‐in groups than in the non‐candidate groups (12.6 and 11.0 months vs. 3.0 and 6.1 months, respectively). The PPS was not significantly different between the REACH‐2‐in and ‐out groups. A significant predictor of candidates for second‐line treatment at sorafenib initiation was a Child–Pugh score of 5 (A5). Conclusions Not all patients refractory to sorafenib were candidates for second‐line therapy. A Child–Pugh score of A5 at sorafenib initiation was an important and favorable factor related to eligibility for second‐line therapy and good outcomes.

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

“…Finally, 8 studies were included in the meta-analysis, enrolling 809 patients [9,[15][16][17][18][19][20][21]. The enrollment period ranged from 2009 to 2019.…”

“…The enrollment period ranged from 2009 to 2019. One study was an RCT [9] and seven non-randomized studies [15][16][17][18][19][20][21]. Two studies were comparative series [9,20], and included studies were conducted mostly in Asia.…”

“…Overall survival was reported in seven studies [9,[15][16][17][19][20][21]. Median OS was 11.08 months (95% CI: 9.46-12.71), with moderate evidence of heterogeneity (I 2 = 45.5%; Figure 2).…”

Analyses of objective response rate, progression‐free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study

“…Nowadays, regorafenib improves the overall survival of patients with progressive disease receiving sorafenib treatment, and ramucirumab also provides a better survival benefit in patients with serum levels of α‐fetoprotein ≥400 ng/mL who previously received sorafenib compared with placebo . A retrospective study showed that 35.0% and 23.3% of patients receiving sorafenib treatment were candidates for regorafenib and ramucirumab, respectively …”

“…9,10 A retrospective study showed that 35.0% and 23.3% of patients receiving sorafenib treatment were candidates for regorafenib and ramucirumab, respectively. 11 Lenvatinib (Lenvima; Eisai, Tokyo, Japan), which is an oral multikinase inhibitor, acts as a blockade of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor-α, KIT, and RET. [12][13][14] The phase II study of lenvatinib showed the objective response rate (ORR) of 37%, tumor shrinkage in 80% of patients, and acceptable toxicity profile.…”