Real‐world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian Center

Abstract

Introduction: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety, however, are lacking. Methods:We conducted a retrospective review of all patients with advanced HCC seen at our center who received at least one dose of an ICI between May 2015 and June 2018. Data cutoff was December 31, 2018. Responses were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Results:Of 114 patients, 88.6% were male. Median age was 66 years, 96.5% had an Eastern Cooperative Oncology Group of 0-1. 62.3% received monotherapy ICI. 18.4% of patients had Child-Pugh (CP) B disease on initiation of ICI, and 69.3% had an ALBI grade of 2. 54.4% were known to have chronic hepatitis B (HBV) or were previously infected, and 11.4% had hepatitis C. Baseline HBV viral load (VL) ranged from undetectable to 8 210 000 IU/mL. 35.1% received prior systemic treatment. 28.9% received prior sorafenib. Over a median follow-up duration of 13.8 months (10.4-15.8), ORR was 18.4%, and DCR was 50.9%. Median progression-free survival was 2.7 months (1.3-4.0), and median overall survival (OS) was 13.9 months (6.9-16.2). Thirty-one patients (27.2%) received further systemic therapy after ICI discontinuation. On multivariable analyses, lower albumin level, higher bilirubin level, diuretic-refractory ascites, and HBV-associated HCC were associated with poorer OS. 69.3% of patients experienced adverse events (AE) of any grade, 14.9% of these being grade 3-4. No grade 5 AE were observed. Use of antiviral therapy was associated with a lower risk of grade 3 or above hepatic AEs (P = 0.048), whereas high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AE. Discussion:We have demonstrated that the real-world performance of ICIs in advanced HCC appears comparable to that observed in clinical trials for HCC patients with CP A cirrhosis. While prognosis of patients with advanced HCC and CP B cirrhosis remains poor even with ICI, usage of ICI is likely to be safe. Patients with HBV with a baseline HBV VL ≥100 IU/mL may receive ICI safely, especially if they are on antiviral treatment.

<p>Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma</p>

“…OncoTargets and Therapy 2020:13 prognosis remains poor and the rate of irAEs always higher than patients with Child-Pugh class A HCC, usage of ICI is likely to be safe. 41,42 The treatment strategy for CPB HCC warrants further investigation. Here, we will describe the most common irAEs associated with ICCtreated HCC patients and discuss screening and monitoring strategies based on the general guidelines provided by SITC, ASCO, NCCN, and ESMO.…”

Adverse events of immune checkpoint inhibitors in advanced hepatocellular carcinoma and their prognostic significance

“…describing real-world data on the efficacy and safety of immune checkpoint inhibitor (ICI) in advanced hepatocellular carcinoma (HCC) patients. 1 They found that the real-world performance of ICIs in advanced HCC appears comparable to that observed in clinical trials for HCC patients with Child-Pugh class A cirrhosis.…”

Real‐world evidence in hepatocellular carcinoma

“…An observational study confirmed the safety and efficacy of nivolumab across various lines of therapy 49 . The use of immune checkpoint inhibitors (ICI) in advanced HCC has been shown to be a comparable to that in HCC patients with Child‐Pugh A cirrhosis 50 …”

“…49 The use of immune checkpoint inhibitors (ICI) in advanced HCC has been shown to be a comparable to that in HCC patients with Child-Pugh A cirrhosis. 50 Lenvatinib has been shown to be an effective second-line therapy in a number of real-world settings. 37,[51][52][53] TA B L E 1 Systemic therapies for the treatment of hepatocellular carcinoma a drug combination recently approved by the FDA, has been shown to markedly improve overall survival and progression-free survival compared to sorafenib, and real-world studies are expected.…”