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Multicenter Study
. 2023 Jul;149(7):3065-3073.
doi: 10.1007/s00432-022-04206-8. Epub 2022 Jul 21.

Ipilimumab and nivolumab in advanced hepatocellular carcinoma after failure of prior immune checkpoint inhibitor-based combination therapies: a multicenter retrospective study

Daniel Roessler  1   2 , Osman Öcal  3 , Alexander B Philipp  4 , Daniel Markwardt  4 , Stefan Munker  4 , Julia Mayerle  4   5 , Leonie S Jochheim  6 , Katharina Hammer  4 , Christian M Lange  4   6 , Andreas Geier  7 , Max Seidensticker  3 , Florian P Reiter  7 , Enrico N De Toni  4 , Najib Ben Khaled  4   8
Affiliations
Multicenter Study

Ipilimumab and nivolumab in advanced hepatocellular carcinoma after failure of prior immune checkpoint inhibitor-based combination therapies: a multicenter retrospective study

Daniel Roessler et al. J Cancer Res Clin Oncol. 2023 Jul.

Abstract

Introduction: Immune checkpoint inhibitor (ICI)-based regimens are transforming the landscape of hepatocellular carcinoma (HCC) treatment. We describe the effect of combined ipilimumab and nivolumab in patients with advanced HCC after the failure of prior ICI-based combination treatments.

Methods: The clinical course of patients with advanced HCC who received combined ipilimumab and nivolumab after prior ICI-based combination therapies was assessed. Progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) per RECIST v1.1 and mRECIST, overall survival (OS), and safety were analyzed.

Results: Of 109 patients treated with atezolizumab and bevacizumab or other ICI-based combination treatments, ten patients received subsequent therapy with ipilimumab and nivolumab. The majority of patients had Barcelona Clinic Liver Cancer (BCLC) Stage C (80%) HCC and a preserved liver function as defined by Child-Pugh A (80%). At a median follow-up of 15.3 months, ORR for ipilimumab and nivolumab was 30% with a DCR of 40%. Median PFS was 2.9 months and the median OS was 7.4 months.

Conclusion: This retrospective study demonstrates that combined ipilimumab and nivolumab can be effective and tolerable after prior ICI-based combination therapies and provides a rationale for the prospective clinical evaluation of this treatment sequencing.

Keywords: Atezolizumab; Bevacizumab; Hepatocellular carcinoma; Immune checkpoint inhibitors; Ipilimumab; Nivolumab.

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Conflict of interest statement

DR advises for Bayer and advises and has received grants from Ipsen. SM received a research grant from Ipsen. MS reports lecture honorarium from Siemens, Cook medical, Boston Scientific, LIAM, Bayer, Sirtex and research grants from Sirtex and Bayer. FPR has received honoraria for lectures and travel support from the Falk Foundation, Gilead and Novartis. AG has received honoraria for lectures, teaching, advisory activities and travel support from AbbVie, Alexion, Bayer, BMS, CSL Behring, Eisai, Gilead, Intercept, Falk, Ipsen, MSD, Merz, Novartis, Pfizer, Roche, Sanofi-Aventis, Sequana and has received research support from Intercept und Falk (NAFLD CSG) and Novartis. EDT has served as a paid consultant for AstraZeneca, Bayer, BMS, EISAI, Eli Lilly & Co, Pfizer, IPSEN, and Roche. He has received reimbursement of meeting attendance fees and travel expenses from Arqule, Astrazeneca, BMS, Bayer, Celsion and Roche, and lecture honoraria from BMS and Falk. He has received third-party funding for scientific research from Arqule, AstraZeneca, BMS, Bayer, Eli Lilly, and Roche. LSJ has received speaker honoraria from Boston. NBK has received reimbursement of meeting attendance fees and travel expenses from EISAI and lecture honorarium from Falk. All the other authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Kaplan–Meier analysis of progression-free survival of patients with advanced HCC treated with ipilimumab and nivolumab after the failure of prior PD-1/PD-L1 inhibitor-based combination therapy. PFS progression-free survival
Fig. 2
Fig. 2
Kaplan–Meier analysis of overall survival of patients with advanced HCC treated with ipilimumab and nivolumab after the failure of prior PD-1/PD-L1 inhibitor-based combination therapy. OS overall survival
Fig. 3
Fig. 3
Swimmers blot illustrating the clinical course of 10 patients with advanced HCC treated with sequential combination immunotherapy. The blot depicts the time from initiation of PD-1/PD-L1 inhibitor-based combination therapy followed by ipilimumab and nivolumab until progression or death. The name of the combination therapy prior to ipilimumab and nivolumab (atezolizumab + bevacizumab or nivolumab + lenvatinib) is indicated at the beginning of the y-axis
See this image and copyright information in PMC

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