Real-World Outcomes of Nivolumab in Patients With Unresectable Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus Infection

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.

A Real-World Comparative Analysis of Lenvatinib and Sorafenib as a Salvage Therapy for Transarterial Treatments in Unresectable HCC

“…Radiologic responses were determined by two certified radiologists and classified according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) [ 26 , 27 , 28 ]. The first response evaluation was performed using computed tomography or magnetic resonance imaging (MRI) 4–8 weeks after drug administration, and further evaluations were performed every 8 weeks thereafter.…”

The Role of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review and Pooled Analysis of 2,402 Patients

“…This included 11 clinical trials (4 randomized and 7 nonrandomized) and 8 cohort studies (Table 1), 12 case series, and 32 case reports (supplemental online Table 3). Fifty of the articles described the use of immunotherapy agents in the setting of unresectable HCC [13, 14, 18, 29–75], 3 in the neoadjuvant setting [76–78], and 10 in the setting of LT [79–88], and they reported on 2,402 patients in total (Fig. 1).…”

“…The score of the modified Jadad scale for the RCTs [18, 54, 59, 63] was 6.5 ± 0.9 (supplemental online Table 4). The mean score of the NOS scale for the nonrandomized studies [13, 14, 30, 35, 36, 42, 45, 53, 56–58, 60, 66, 70, 73] was 7.4 ± 0.6 (supplemental online Table 5). The mean score of the NHBLI scale for the case series [31, 32, 37, 39, 40, 44, 51, 62, 67, 77, 80, 84] was 6.8 ± 0.9 (supplemental online Table 6).…”

Diffusion-Weighted Magnetic Resonance Imaging in Hepatocellular Carcinoma as a Predictor of a Response to Cisplatin-Based Hepatic Arterial Infusion Chemotherapy

“…However, these drugs only have modest treatment responses and may even have notable side effects (3,4). Furthermore, the latest immune checkpoint inhibitor monotherapy did not demonstrate increased survival compared with sorafenib in patients with unresectable HCC (5).…”