Programmed cell death protein 1 (PD-1)-inhibition in hepatocellular carcinoma (HCC): a single center experience

Abstract

Background

The prognosis for advanced Hepatocellular carcinoma (HCC)is still very poor. Despite initial usefulness of immune checkpoint inhibitor (PD-1), phase 3 trials failed to show significant benefit of PD-1 inhibition with nivolumab or pembrolizumab in the first and second line therapy of HCC. Clinical evidence of PD-1 inhibition in patients with advanced and heavily pretreated HCC outside clinical trials is extremely limited. In this study, we analyzed the clinical experience with PD-1 inhibition in patients with heavily pretreated HCC.

Methods

Between May 2016 and January 2019 14 patients with advanced and heavily pretreated HCC were treated with nivolumab or pembrolizumab at the University Hospital Bonn, Germany. Base line characteristics prior to immunotherapy, immunohistochemistry of different immunological markers, beneficial outcome and safety were recorded and retrospectively analyzed.

Results

Immunotherapy with PD-1 inhibition was well tolerated and resulted in significant clinical benefit as last line therapy. Median overall survival (OS) was 6.6 months (95%CI:3.9–11.8), progression-free survival (PFS) was 5.3 months (95%CI:2.4–11.7) and overall response rate (ORR) was 30.8%. One patient reached a complete remission.

Conclusions

Despite numerous pretreatments, PD-1 inhibition was well tolerated and showed clinical benefit in patients with heavily pretreated HCC.

Keywords:

• Hepatocellular carcinoma
• immune checkpoint inhibition
• nivolumab
• PD-1 inhibition
• pembrolizumab

Acknowledgements

The authors thank Ms. Kathrin Brinkmann and Ms. Sonja Hebold for their extremely valuable support and assistance in this work.

Disclosure statement

All authors approved the final version of the manuscript. None of the authors have any potential conflicts (financial, professional or personal) that are relevant to the manuscript. Maria A. Gonzalez-Carmona has contributed to advisory board for BMS, Eisai, Amgen, IPSEN and Roche.

Additional information

Funding

This work was supported by the following grants awarded to M.A. Gonzalez-Carmona: GO 1874/1-2 grant from the ‘Deutsche Forschungsgemeinschaft’ (DFG), BONFOR from the University of Bonn, grant number 109255 from the ‘Deutsche Krebshilfe’ (German Cancer Aid) and grant from the Reuthersche endowment fund of the University of Bonn.