Abstract 188P
Background
Resistance to atezolizumab/bevacizumab is common among patients with hepatocellular carcinoma (HCC) and a relevant proportion of patients experiences treatment-related toxicity. Given these outcomes, it is essential to identify patients who are not likely to benefit from treatment with atezo/bev. This study aims to analyze the frequency and risk factors of early mortality (EM) in HCC patients treated with atezo/bev.
Methods
This retrospective study uses data from a large, European real-world cohort and flow cytometry-based immunophenotyping of patient PBMCs. EM was defined as death from any cause within 90 days of treatment initiation. Uni- and multivariable logistic regression analysis was used to identify clinical and laboratory parameters associated with EM.
Results
334 patients with unresectable HCC treated with first-line atezo/bev and sufficient follow-up of 90 days were included. EM rate in the cohort was 18.7%. In the EM cohort, a lower proportion of patients with preserved liver function and BCLC stage B could be observed, while CHILD-Pugh (CP) C and BCLC D were significantly more frequent. The strongest predictor of EM was moderate to severe liver disease in univariate analysis, as reflected by surrogates of impaired liver function such as CP B (OR 2.7, p = 0.007), CP C (OR 37, p < 0.001), ALBI grade 2 / 3 (OR 12, p = 0.02/ OR 120, p = 0.002), high MELD score (OR 1.3, p = 0.002), high bilirubin (OR 4.5, p = 0.008), and low albumin (OR 7.0, p = 0.003). CP B and C remained significant risk factors after adjusting for other variables. Other significant risk factors of EM included prior variceal bleeding (OR 4.7, p = 0.006), high leucocyte count (OR 1.3, p = 0.02), and high neutrophil count (OR 1.4, p = 0.02). Immunophenotyping of PBMC (n = 40) revealed reduced lymphocyte frequencies as well as increased CD44 expression on regulatory T cells (Treg) to be associated with EM.
Conclusions
EM is frequent in patients with HCC treated with atezo/bev. Significant risk factors for early death involved impaired liver function, elevated biomarkers of inflammation and alterations of systemic immunity, but not reduced performance status, age or characteristics of advanced cancer such as extrahepatic spread, macrovascular invasion, or elevated AFP.
Legal entity responsible for the study
University Hospital, LMU Munich, Munich, Germany.
Funding
Has not received any funding.
Disclosure
N. Ben Khaled: Financial Interests, Personal, Invited Speaker: Falk, AstraZeneca, Eisai. L. Jochheim: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, AbbVie, Falk, Boston Scientific; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca. K. Boettcher: Financial Interests, Personal and Institutional, Invited Speaker: Ipsen. B. Scheiner: Financial Interests, Institutional, Research Grant: AstraZeneca, Eisai; Financial Interests, Personal and Institutional, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Other, travel support: AbbVie, AstraZeneca, Ipsen, Gilead. S.J. Gairing: Financial Interests, Personal and Institutional, Other, travel support: Gilead, Ipsen. O. Oecal: Financial Interests, Personal and Institutional, Other, honorarium: Bayer. U. Ehmer: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Falk, Ipsen, Novartis; Financial Interests, Personal and Institutional, Other, travel support: AstraZeneca, Biotest; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bayer, Eisai, MSD. M. Venerito: Financial Interests, Personal and Institutional, Other, honoraria: Amgen, AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, Merck, MSD, Nordic Pharma, Roche, Servier, Sirrten. F. Foerster: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, MSD, Pfizer, Roche, Servier; Financial Interests, Personal and Institutional, Other, travel support: Merck, Servier; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, BMS, Eisai, Roche. M. Pinter: Financial Interests, Personal and Institutional, Invited Speaker: Bayer, BMS, Eisai, Ipsen, Lilly, Roche, MSD; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, Roche, MSD; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Bayer, BMS, Eisai, Roche; Financial Interests, Personal and Institutional, Other, travel support: Bayer, BMS, Ipsen, Roche. A. Geier: Financial Interests, Personal and Institutional, Advisory Board: AbbVie, Alexion, Bayer, BMS, CSL Behring, Eisai, Falk, Gilead, Heel, Intercept, Ipsen, Merz, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, Sequana; Financial Interests, Personal and Institutional, Invited Speaker: Advanz. E.N. De Toni: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bayer, BMS, Eisai, Lilly, Pfizer, Ipsen, Roche; Financial Interests, Personal and Institutional, Other, travel support: Arqule, AstraZeneca, BMS, Bayer, Celsion, Roche; Financial Interests, Personal and Institutional, Invited Speaker: BMS, Falk, Arqule; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, BMS, Bayer, Lilly, Roche. F.P. Reiter: Financial Interests, Personal and Institutional, Other, honoraria: Falk, AbbVie, Gilead, Ipsen, AstraZeneca, Roche, Novartis. All other authors have declared no conflicts of interest.