Effectiveness of nivolumab versus regorafenib in hepatocellular carcinoma patients who failed sorafenib treatment

Abstract

<jats:p>Background/Aims: Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients.Methods: Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias.Results: Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0–10.8) months for regorafenib and 5.9 (95% CI, 3.7–8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30–0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51–1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04).Conclusions: After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.</jats:p>

Clinical outcomes and influencing factors of PD‑1/PD‑L1 in hepatocellular carcinoma (Review)

“…The reason why cemiplimab, atezolizumab, avelumab, durvalumab have not been included in the guidelines for the treatment of HCC is that their efficacy and safety is not completely certain, and several trials are still ongoing (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Nivolumab as a first-line treatment option compared with sorafenib is still under research, and nivolumab may become first-line treatment if the result is positive (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23); atezo+bev has potential as a first-line treatment for unresectable HCC; both avelumab and axitinib are known to be safe when administered as monotherapy; cemiplimab and durvalumab have also demonstrated effectiveness in ORR (30,33,35,37,40). With an increase in the number of clinical trails, cemiplimab, atezolizumab, avelumab and durvalumab may be added to the guidelines.…”

“…However, nivolumab may be more effective than regorafenib in nonprogressors ( 20 ). Research reported that following sorafenib failure, nivolumab treatment is associated with improved OS (overall survival) and ORR compared with regorafenib treatment ( 21 ). Nivolumab plus ipilimumab was evaluated in patients with advanced HCC pretreated with sorafenib.…”

Optimal sequence of systemic therapy after sorafenib failure in patients with hepatocellular carcinoma

“…Although IPTW estimation is now commonly used to control for confounding factors in nonexperimental studies of medical interventions, 11 not all of the confounders could be adjusted. In the study by Lee et al, 9 the median duration of sorafenib treatment was 2.5 months (1.4-3.1) and 3.0 months (2.3-6.2) in the nivolumab and regorafenib groups, respectively (P<0.001). Considering that longer sorafenib treatment duration is associated with better response to regorafenib, and that physicians may prefer regorafenib to nivolumab as the second-line treatment in case of a favorable response to sorafenib, there is a possibility that selection bias which cannot be corrected by IPTW may persist.…”

“…Regarding this issue, Lee et al 9 reported comparable efficacy and safety between nivolumab and regorafenib in patients with advanced disease (Barcelona Clinic Liver Center [BCLC] stage B or C) who had experienced sorafenib failure. Their retrospective study was conducted at a single institution, and most of the enrolled patients had BCLC stage C disease (96.7%).…”

Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma

“…The progression-free survival, overall survival and response rates were found to be better for patients treated with anti-PD-1/PD-L1 compared to placebo [ 25 ]. However, the data from the retrospective analysis did not show differences between anti-PD-1/PD-L1 when compared to regorafenib [ 48 , 49 ]. Interestingly, a combination of anti-PD-1/PD-L1 with radiation therapy showed better progression-free survival and overall survival when compared to anti-PD-1/PDL-1 alone [ 50 ] ( Table 2 ).…”