Programmed cell death protein‐1 (PD‐1)‐targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real‐world cohort

Abstract

Summary Background Programmed cell death protein‐1‐targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. Aim To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real‐world cohort of patients with advanced hepatocellular carcinoma. Methods Sixty‐five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut‐off) across six centres in Austria and Germany were retrospectively analysed. Results Child‐Pugh class A/B/C was 32 (49%)/28 (43%)/5 (8%). Immunotherapy was used as systemic first‐/second‐/third‐/fourth‐line treatment in 9 (14%)/27 (42%)/26 (40%)/3 (5%) patients. Fifty‐four patients had at least one follow‐up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12% and 49% respectively. Of 52 evaluable patients, four (8%) had hyperprogressive disease. Median time to progression was 5.5 (95% CI, 3.5‐7.4) months, median progression‐free survival was 4.6 (95% CI, 3.0‐6.2) months, and median overall survival was 11.0 (95% CI, 8.2‐13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child‐Pugh A and B patients; however, median overall survival (OS) was shorter in Child‐Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first‐/second‐line and third‐/fourth‐line respectively. Conclusions Programmed cell death protein‐1‐targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child‐Pugh stage B and patients with intensive pretreatment.

Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects

“…Real life data on nivolumab in HCC provided by Gomes da Fonseca et al at the 2019 International Liver Congress showed a safety profile consistent with clinical trials, with 42.9% of patients presenting adverse events, and a median overall survival in the patients receiving the drug as a second‐line treatment of 28.8 months since start of first line. Scheiner et al reported a similar rate of adverse events and a median overall survival of 11.0 months in a cohort of advanced HCC treated with nivolumab or pembrolizumab.…”

Letter: programmed cell death protein‐1‐targeted immunotherapy for advanced hepatocellular carcinoma

“…In a study investigating sorafenib for advanced HCC, patients with Child-Pugh B cirrhosis had similar rates of adverse events and shorter overall survival times than those with class A. 2,3 Adverse events among patients with Child-Pugh class C (n = 5) were not reported. A meta-analysis found that 14% of patients who received PD-1 and PD-L1 inhibitors developed at least one adverse event of grade 3 or higher severity.…”

“…4,5 In the present study, 39% of patients experienced at least one adverse event, and the rate of hepatitis was 5%. 2 The second concern is about the treatment line of immunotherapy. No difference was observed in terms of efficacy or adverse events between patients with first/second-line and third/ fourth-line immunotherapy.…”

“…No difference was observed in terms of efficacy or adverse events between patients with first/second-line and third/ fourth-line immunotherapy. 2 Most included patients received sorafenib as first-line therapy, and then received nivolumab or pembrolizumab. A case report found that sorafenib + nivolum-ab+regorafenib provided safe and effective outcome in advanced HCC.…”

“…However, no patients achieved complete response after pembrolizumab or nivolumab. 2 In phase 2 trials, 1% and 4% patients achieved complete response after pembrolizumab 9 or nivolumab. 8…”