PD-1 targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicenter real-world cohort

Background:

Programmed cell death protein-1 (PD-1)-targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma (HCC). We report safety and efficacy data of an international, multicenter, real-world cohort of patients with advanced HCC treated with nivolumab or pembrolizumab.

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 6 centers in Austria and Germany were retrospectively analyzed.

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), diarrhea (n = 3), and hepatitis (n = 3). Efficacy and safety results were comparable between Child-Pugh A and B patients; however, median 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.

Conclusion:

PD-1-targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patient with advanced HCC, including subjects with Child-Pugh stage B and patients with intensive pretreatment.