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

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Programmed cell death protein‐1‐targeted immunotherapy has shown promising results in phase <jats:styled-content style="fixed-case">II</jats:styled-content> studies of hepatocellular carcinoma.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real‐world cohort of patients with advanced hepatocellular carcinoma.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 3.5‐7.4) months, median progression‐free survival was 4.6 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 3.0‐6.2) months, and median overall survival was 11.0 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 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 (<jats:styled-content style="fixed-case">OS</jats:styled-content>) was shorter in Child‐Pugh B patients (16.7 vs 8.6 months; <jats:italic>P</jats:italic> = 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>