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Multicenter Study
. 2020 Aug;8(2):e001033.
doi: 10.1136/jitc-2020-001033.

Post-registration experience of nivolumab in advanced hepatocellular carcinoma: an international study

Petros Fessas  1 , Ahmed Kaseb  2 , Yinghong Wang  3 , Anwaar Saeed  4 , David Szafron  5 , Tomi Jun  6 , Sirish Dharmapuri  6 , Abdul Rafeh Naqash  7 , Mahvish Muzaffar  7 , Musharraf Navaid  7 , Uqba Khan  8 , ChiehJu Lee  9 , Anushi Bulumulle  7 , Bo Yu  10 , Sonal Paul  10 , Neil Nimkar  10 , Dominik Bettinger  11 , Francesca Benevento  12 , Hannah Hildebrand  4 , Tiziana Pressiani  13 , Yehia I Abugabal  2 , Nicola Personeni  13   14 , Yi-Hsiang Huang  9 , Lorenza Rimassa  13   14 , Celina Ang  6 , Thomas Marron  6 , David J Pinato  15
Affiliations
Multicenter Study

Post-registration experience of nivolumab in advanced hepatocellular carcinoma: an international study

Petros Fessas et al. J Immunother Cancer. 2020 Aug.

Abstract

Background: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

Patients and methods: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

Results: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line (n=148, 63.5%). Objective response rate (ORR) was 22.4% and disease control rate was 52.1%. Median overall survival (OS) was 12.2 months (95% CI 8.4 to 16.0) and median progression-free survival was 10.1 months (95% CI 6.1 to 14.2). Treatment-related adverse events of grade >2 occurred in 26 patients (11.2%). Efficacy and safety were similar across CP classes and therapy line. OS was shorter in CP-B than A (7.3 months vs 16.3 months, p<0.001) and in post-first line use (10.4 months vs 16.3 months, p=0.05). Achievement of an objective response predicted for improved OS (25.4 months vs 13.2 months, p<0.001).

Conclusions: This study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.

Keywords: antibodies, neoplasm; immunotherapy; liver neoplasms; programmed cell death 1 receptor.

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Conflict of interest statement

Competing interests: DP received lecture fees from ViiV Healthcare, Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, Astra Zeneca; received research funding (to institution) from MSD, BMS. DB has received lecture and speaker fees from Bayer Healthcare and the Falk Foundation Germany. LR received lecture fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, Sanofi; advisory board/consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi; travel expenses from Ipsen; received research funding (to institution) from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Roche. NP received lecture fees from AbbVie and Gilead; travel expenses from ArQule. YHH has received advisory board/consulting fees for BMS, MSD, Bayer Healthcare, IPSEN, EISAI, Gilead and Lilly. AS received research funding (to institution) from AstraZeneca, Exelixis, BMS and Clovis; advisory board/consulting fees from BMS, AstraZeneca, and Exelixis.

Figures

Figure 1
Figure 1
Flow chart illustrating patient disposition.
Figure 2
Figure 2
The relationship between best radiological response to nivolumab and liver functional reserve by Child-Pugh class (CP, A) and line of therapy (B). CR, complete response; PD, primary disease; PR, partial response; SD, stable disease.
Figure 3
Figure 3
Kaplan-Meier curves describing the overall survival of the whole patient cohort (A) stratified by best radiological response (B) and Child-Pugh (CP) class (C). (D) Patients’ progression-free survival stratified by best radiological response (E). CR, complete response; PD, primary disease; PR, partial response; SD, stable disease.
Figure 4
Figure 4
The distribution of treatment-related adverse events (trAEs) of any grade in relation to etiology of chronic liver disease (viral vs non-viral, A) and Child-Pugh (CP) class (B).
See this image and copyright information in PMC

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