Abstract
Real-world results of nivolumab monotherapy against HCC are lacking in the hepatitis B virus (HBV)-endemic, Asia-Pacific regions. Moreover, heterogeneous responses to immune checkpoint inhibitors have rarely been described in advanced HCC. The aim of this study is to evaluate the efficacy and safety of nivolumab monotherapy in a real-world setting in 33 Korean patients with unresectable HCC. In our cohort, twenty-nine patients (88%) showed HBsAg positivity. At the time of nivolumab initiation, 4 among 33 patients (12%) were classified as Barcelona Clinic Liver Cancer (BCLC)-B stage and 29 (88%) as BCLC-C stage, respectively. Prior sorafenib treatment was given to 31 (94%) patients, and 13 (39%) received prior regorafenib treatment. For the liver reserve, patients were classified as Child–Pugh class A (79%) and B (21%), respectively. Grade 3 toxicities occurred in one patient, who developed pneumonitis after 5 cycles of nivolumab treatment. Best overall responses were complete response in 2 patients out of the 33 enrolled patients (6%), partial response in 4 patients (12%) and stable disease in 4 patients (12%). With 29 patients having images for the response evaluation, the objective response rate was 21.4%. The median overall survival (OS) of the cohort was 26.4 weeks (range 2.3–175.1). Achieving objective responses, pre-treatment small tumors (maximal diameter <5 cm) and favorable liver function as assessed by Albumin–Bilirubin grade were significant factors for the favorable OS. Interestingly, differential responses to nivolumab among multiple tumors in a single patient were noted in 6 patients (18%). In these patients, small metastatic tumors were regressed, although their larger tumors did not respond to nivolumab monotherapy. In summary, nivolumab treatment seems clinically efficacious in treating unresectable HCC in an endemic area of HBV infection. Further prospective evaluation is required to overcome the heterogeneous efficacy of nivolumab monotherapy according to the baseline tumor burden.
Highlights
Worldwide, hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality
Clinical trials with nivolumab and pembrolizumab in unresectable HCC, representative anti-PD-1 antibodies, had been anticipated to show prolonged survivals in patients treated with these drugs
Unlike other solid tumors, there was no marked association identified between the levels of tumor cell programmed death-ligand 1 (PD-L1) expression and responses to nivolumab in HCC, reported by earlier Keynote-224 and CheckMate-040 studies [5, 11, 12]
Summary
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality. Three tyrosine kinase inhibitors have demonstrated improved outcomes: lenvatinib in the first-line, and regorafenib and cabozantinib after first-line failure [4]. They showed some promising results in terms of efficacy, their use may be limited due to the adverse effects and the potential decrease in the liver reserve. Clinical trials with nivolumab and pembrolizumab in unresectable HCC, representative anti-PD-1 antibodies, had been anticipated to show prolonged survivals in patients treated with these drugs. A phase 3 randomized, multi-centre study (CheckMate 459) evaluating nivolumab monotherapy versus sorafenib as a first-line treatment of unresectable HCC, did not achieve its primary endpoint of overall survival (OS) [9, 10]. There are no validated biomarkers for HCC immunotherapy [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
