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

Pil Soo Sung, Jeong Won Jang, Jaejun Lee, Soon Kyu Lee, Hae Lim Lee, Hyun Yang, Hee Chul Nam, Sung Won Lee, Si Hyun Bae, Jong Young Choi, Nam Ik Han, Seung Kew Yoon, Pil Soo Sung, Jeong Won Jang, Jaejun Lee, Soon Kyu Lee, Hae Lim Lee, Hyun Yang, Hee Chul Nam, Sung Won Lee, Si Hyun Bae, Jong Young Choi, Nam Ik Han, Seung Kew Yoon

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.

Keywords: hepatocellular carcinoma; nivolumab; objective response; tumor heterogeneity; tumor size.

Copyright © 2020 Sung, Jang, Lee, Lee, Lee, Yang, Nam, Lee, Bae, Choi, Han and Yoon.

Figures

Figure 1
Figure 1
Changes in target lesions from the baseline after nivolumab monotherapy. Dashed lines represent a 20% increase or a 30% reduction. The percentage changes more than 100% were truncated to 100% (asterisks) .
Figure 2
Figure 2
Overall survival of patients according to the various clinical parameters. (A) Overall survival of patients according to the tumor response. (B) Overall survival of patients according to the tumor size. (C) Overall survival of patients according to the AFP. (D) Overall survival of patients according to the ALBI grade. (E) Overall survival of patients according to the CPS. AFP, alpha fetoprotein; ALBI grade, albumin-bilirubin grade; CPS, Child-Pugh score; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.
Figure 3
Figure 3
Representative imaging data of a patient with heterogeneous responses to nivolumab. (A) Liver imaging findings after 4 cycles of nivolumab. (B) Lung imaging findings after 4 cycles of nivolumab.

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