For patients with hepatocellular carcinoma treated in the second-line setting, the combination of regorafenib and nivolumab following 2 cycles of regorafenib monotherapy appeared safe, according to phase 1/2a study.
The combination of regorafenib (Stivarga) and nivolumab (Opdivo) following 2 cycles of regorafenib monotherapy was associated with a manageable safety profile in patients with hepatocellular carcinoma (HCC) treated in the second-line setting, according to fi ndings from the phase 1/2a GOING trial (NCT04170556).
Less than one-third of patients in the study developed grade 3/4 treatment-related adverse events (AEs) and no treatment related deaths were reported, according to findings presented at the European Association for the Study of the Liver Liver Cancer Summit 2022. Current options for first-line treatment are sorafenib and atezolizumab-bevacizumab.
The GOING trial assessed the safety profile of regorafenib and nivolumab in patients with HCC who progress on or after sorafenib (Nexavar) but tolerate treatment (cohort A, n = 60) or who had to discontinue atezolizumab (Tecentriq) plus bevacizumab (Avastin; cohort B, n = 18).
“The primary aim of the study is safety, measured in terms of rate of AEs, rate of treatment-related AEs, rate of AEs leading to treatment discontinuation, and rate of death,” Marco Sanduzzi-Zamparelli, MD, of the Barcelona Clinic Liver Cancer (BCLC) group at the Hospital Clinic of Barcelona, said in a presentation of the data.
Researchers created a treatment schedule where the patients received 160 mg of singleagent regorafenib per day for 8 weeks (3 weeks on and 1 week off). Afterward, the combination phase was initiated with regorafenib at the tolerated dose at week 8 with 240 mg of nivolumab given every 2 weeks. Treatment was discontinued at any point if a patient experienced toxicity, symptomatic progression, or death, or if they wished to discontinue.
The researchers also planned a futility analysis for when there are tumor assessment data for 32.8% of cohort A, based on RECIST v1.1 criteria by at least week 16.
In terms of baseline characteristics of the patients from cohort A who were included in the interim analysis (n = 30), there was a median age of 65 years (range, 58-72), most were male (86%), and the most frequent etiology was hepatitis C virus (n = 12) followed by nonalcoholic fatty liver disease (n = 9), alcohol (n = 4), normal liver (n = 4), and hepatitis B virus (n = 1). More than half of patients had cirrhosis (n = 16), with good performance status and good liver function.
Most patients (76.7%) had BCLC stage C and 23.3% had stage B. There were 11 patients with extrahepatic disease and 17 with vascular invasion. Seven patients had BCLC post progression (BCLCpC2).
All patients experienced treatmentemergent AEs of any cause, with 96.7% experiencing treatment-related AEs. Severe treatment-emergent AEs were seen in 14 patients and severe treatment-related AEs were seen in 10. There were 4 patients with serious treatment-related AEs related to both regorafenib and nivolumab, 3 specifi cally related to just regorafenib and 3 to nivolumab. Eight patients had treatment-related AEs leading to treatment interruption. Finally, there were 4 severe AEs of special interest.
In the profile of treatment-related AEs occurring in more than 10% of the patients, handfoot-skin reactions were the most frequent AE (any grade, n = 17; grade 3, n = 3). This was followed by asthenia (any grade, n = 13; grade 3, n = 0), diarrhea (any grade, n = 11; grade 3, n = 1), decreased appetite (any grade, n = 9; any grade 3, n = 0), arterial hypertension (any grade, n = 9; grade 3, n = 2) hypertransaminasemia (any grade, n = 9; grade 3, n = 1), hyperbilirubinemia (any grade, n = 6; grade 3, n = 1), an increase of aspartate aminotransferase (any grade, n = 6; grade 3, n = 1), abdominal pain (any grade, n = 6; grade 3, n = 0), dysphonia (any grade, n = 5, grade 3, n = 0), and an increase in alanine aminotransferase (any grade, n = 4; grade 3, n = 0). No grade 4 or 5 treatment-related AEs were reported.
The reasons for study discontinuation in patients were physician decision (n = 4), progressive disease (n = 2), and AEs (n = 2), one of which was treatment related. “It is worth a mention that one case (of the physician decision study discontinuation) was due to surgical rescue after achieving partial response,” Sanduzzi-Zamparelli said. The futility analysis in cohort A was based on objective response rate.
“The sequential combination of regorafenib and nivolumab after 2 cycles of regorafenib priming has a manageable safety profile,” Sanduzzi-Zamparelli explained. “Less than one-third of the patients developed grade 3/4 treatment-related adverse event and there was no treatment-related death, and the futility analysis allowed to continue recruitment.”