111P - Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma compared to patients with advanced solid tumours

Background

Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). In this comparative study, we aimed to compare incidence, clinical characteristics and outcomes of irLI between patients receiving ICIs for HCC versus other solid tumour indications.

Methods

Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line Atezolizumab+Bevacizumab from AB-real study and a non-HCC cohort, including 459 patients treated with first-line ICI therapy from INVIDIa-2 multicentre study. IrLI was defined as treatment-related increase of transaminases levels after exclusion of alternative aetiologies of liver injury. Incidence of irLI was adjusted for the duration of treatment exposure.

Results

In HCC patients, incidence of any-grade irLI was 11.4% over a median treatment exposure of 4.4 months (95%CI 3.7-5.2), compared to 2.6% in INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95%CI 11.1-14.0). Exposure-adjusted incidence of any-grade irLI was 22.1 per 100-Patient-years (PY) in HCC patients and 2.1 per 100-PY in non-HCC patients (p<0.001), with median time to irLI of 1.4 in HCC and 4.7 months in non-HCC patients, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of HCC and in 75.0% of non-HCC patients (p<0.001) and irLI resolution was observed in 72.1% and 58.3%, respectively (p=0.362). In HCC patients, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. In both cohorts, no fatal irLI events occurred. Development of grade 1-2 irLI was associated with improved overall survival in HCC patients only (HR 0.53, 95%CI 0.29-0.96).

Conclusions

Despite higher incidence and earlier onset in patients with HCC, IrLI is characterised by high rates of remission, low requirement for corticosteroid therapy and low risk of decompensation compared to other solid tumours. Hepatotoxicity leads to discontinuation in 7% of patients with HCC and does not negatively affect oncological outcomes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Celsa: Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, AstraZeneca, MSD. G. Cabibbo: Financial Interests, Personal, Advisory Board: Bayer, Eisai, Ipsen, MSD, AstraZeneca, Roche. T.U. Marron: Financial Interests, Personal, Advisory Board: Rockfeller University, Regeneron, AbbVie, Merck, Bristol Myers Squibb, Boehringer Ingelheim, Atara, AstraZeneca, Genentech, Celldex, Chimeric, DrenBio, GlenMark, Simcere, Surface, G1 Therapeutics, NGMBio, DBV Technologies, Arcus, Astellas; Financial Interests, Personal, Research Grant: Regeneron, Bristo-Myers Squibb, Merck, Boehringer Ingelheim. A. Saeed: Financial Interests, Personal, Research Grant: AstraZeneca, Bristol Myers Squibb, Merck, Clovis, Exelixis, Actuate Therapeutics, Incyte Corporation, Daiichi Sankyo, Five Prime Therapeutics, Amgen, Innovent Biologics, Dragonfly Therapeutics, KAHR Medical, BioNtech; Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Bristol Myers Squibb, Exelixis, Taiho, Pfizer. M. Pinter: Financial Interests, Personal, Advisory Board: Bayer, Bristol Myers Squibb, Eisai, Ipsen, Lilly, MSD, Roche; Financial Interests, Personal, Non remunerated activity: Bayer, Bristol Myers Squibb. A. Pillai: Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, Exelixis, Genentech/Roche, AstraZeneca, Replimune. M. Schoenlein: Financial Interests, Personal, Other: Janssen, Ipsen, BMS, Astellas, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen. J. von Felden: Financial Interests, Personal, Advisory Board: Roche. P.R. Galle: Financial Interests, Personal, Advisory Board: Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, Lilly, Merck Sharp and Dome, Roche, Sirtex; Financial Interests, Personal, Research Funding: Bayer, Roche; Financial Interests, Personal, Expert Testimony: Lilly; Financial Interests, Personal, Other: AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, Lilly, Roche. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Bayer, Takeda, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, EA Pharma, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AstraZeneca, Basilea, Bayer, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, Elevar Therapeutics, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche; Financial Interests, Institutional, Coordinating PI, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Local PI: Agios, Eisai, Fibrogen, Lilly, MSD; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Coordinating PI, European PI: AstraZeneca; Non-Financial Interests, Personal, Leadership Role, Treasurer: ILCA; Non-Financial Interests, Personal, Leadership Role, Co-chair: EORTC GITCG HB/NET Task Force; Non-Financial Interests, Personal, Other, Special Expert Clinical Trials Europe: NCI HB Task Force. A. Singal: Financial Interests, Personal, Advisory Board: Genentech, AstraZeneca, Eisai, Bayer, Exelixis, BMS, Roche, Glycotest, Exact Sciences, FujiFilm Medical Sciences, GRAIL. H. Chon: Financial Interests, Personal, Advisory Board: Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, Sillajen, Menarini, GreenCross Cell. M. Bersanelli: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Ipsen; Financial Interests, Personal, Other, Case report with copyright transfert: Pierre Fabre; Financial Interests, Institutional, Other, Research funding: Roche, Seqirus, Pfizer, Novartis; Financial Interests, Personal, Writing Engagement: Pierre Fabre, Sciclone Pharmaceuticals; Financial Interests, Personal, Invited Speaker: MSD, Novartis; Financial Interests, Institutional, Local PI: Pfizer; Non-Financial Interests, Personal, Product Samples, congresso grant and accomodation: Pierre Fabre. A. Cortellini: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, OncoC4, Ardelis Health, Access Infinity, AlphaSight; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Pierre Fabre; Financial Interests, Personal, Writing Engagement: MSD, BMS. D.J. Pinato: Financial Interests, Personal, Advisory Board: Mina Therapeutics, Eisai, Exact Sciences, MURSLA, H3B, DaVolterra, AstraZeneca, Bayer Healthcare; Financial Interests, Personal, Invited Speaker: BMS, IPSEN, Roche; Financial Interests, Personal, Other, Editor in Chief role: Wiley; Financial Interests, Institutional, Research Grant: BMS, MSD; Non-Financial Interests, Personal, Principal Investigator: Incyte, H3B, Starpharma, Roche, Ribon Therapeutics, Turning Point Therapeutics, Apollomics; Non-Financial Interests, Personal, Other, Charity Trustee: Cancer Treatment and Research Trust. All other authors have declared no conflicts of interest.