Efficacy of immune checkpoint inhibitors in patients with HIV-associated unresectable HCC (uHCC): Propensity-score matched analyses from two international consortia.

Authors

null

Claudia A.M. Fulgenzi

Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom

Claudia A.M. Fulgenzi , Talal El Zarif , Amin Nassar , Elio Adib , Joaquim Bellmunt , Thomas Urban Marron , Michael Lorentsen , Rana R. McKay , Javier Baena , Celina Ang , Lorenza Rimassa , Masatoshi Kudo , Alessandro Parisi , Anwaar Saeed , Pei-Chang Lee , Neehar Parikh , Matthias Pinter , Alessio Cortellini , Abdul Rafeh Naqash , David James Pinato

Organizations

Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Yale Cancer Center, New Haven, CT, Brigham and Women's Hospital, Boston, MA, Dana-Farber Cancer Institute, Boston, MA, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, UNC Health Care, Chapel Hill, NC, University of California, San Diego, La Jolla, CA, Hospital Universitario 12 De Octubre, Madrid, Spain, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, Humanitas Cancer Center, Rozzano, Italy, Kindai University Faculty of Medicine, Osaka, Japan, Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy, University of Kansas Cancer Center, Westwood, KS, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, University of Michigan, Ann Arbor, MI, Hepatology AKH, Medical University of Vienna, Vienna, Austria, Division of Surgery and Cancer, Imperial College, London, United Kingdom, Stephenson Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK, Imperial College, London, United Kingdom

Research Funding

No funding sources reported

Background: HIV-associated HCC is an incompletely characterized disease with poor prognosis. People living with HIV (PWH) are commonly excluded from clinical trials, leading to a paucity of high-level evidence for optimal management. Whether ICIs are tolerated and effective in HIV-associated uHCC remains unclear. Methods: Using data from the CATCH-IT consortium and from a global dataset recruiting patients with HCC from 14 centers in 3 continents, we selected patients with HIV-associated uHCC treated with ICIs and compared their outcomes with a matched cohort of HIV negative (HIV-) patients. Primary endpoints were overall (OS) and progression-free survival (PFS). Propensity score matching (PSM) between the two groups was performed for the following variables: age, sex, HCC aetiology, Child-Pugh class (CP-C), ECOG-PS, BCLC stage, alpha-fetoprotein (AFP) levels, treatment line, portal vein tumor thrombosis (PVTT), and extrahepatic spread (EHS). Restricted mean survival time (RMST) difference analyses stratified by HIV status were performed for OS and PFS at 3, 6 and 9 months. Results: We accrued 46 PWH and 400 HIV-, treated mostly in the first-line setting (58.7% vs. 43.7%) with either atezolizumab plus bevacizumab (28.3% vs 17.5%) or anti-PD-1 monotherapy. Median age at ICI start was 62 (38-76) and 64 (18-87); viral hepatitis (HCV: 58.7%; HBV: 34.8%) were the prevalent aetiologies in PWH, non-viral (46%) was the most common in HIV-; most patients had BCLC-C HCC (84.8% and 82.3%). In PWH, median CD4 count was 345 cells/mm3 (IQR: 200-465); viral load was undetectable in 45 patients, all were established on combined anti-retroviral therapy. Following PSM, 44 PWH and 117 HIV- were included. Median OS was 7.5 months (95%CI: 5.2-NR) in PWH and 10.8 months (95%CI: 7.3-19.5) in HIV- (HR: 0.89; 95%CI: 0.56-1.42; p=0.58). Presence of PVTT, AFP>400 ng/mL, and ECOG-PS=1 but not HIV status were associated with worse OS in uni- and multivariable models. Median PFS was 2.8 months (95%CI: 2.6-4.8) for PWH vs 3.0 months (95%CI: 2.4-5.3) for HIV- (HR: 0.83-95%CI:0.56-1.24 ;p=0.38); HIV status was not associated with worse PFS. RMST confirmed no OS or PFS differences based on HIV status. In matched cohorts, neither ORR (21% vs. 19.1%, p=0.97) nor DCR (44.7% vs. 55.4%, p=0.19) were associated with HIV status. All grade immune-related adverse events (irAEs) were more frequent in HIV (44.0% vs 21.7%, p=0.003), with similar incidence of grade ≥3 irAEs (22.2% vs 13.0%). PWH had lower incidence of dermatological toxicities (4.3% vs 22%, p=0.003) and a trend towards lower incidence of hepatotoxicity (6.5% vs 18%, p=0.059). Conclusions: This study provides practice-informing evidence to support the use of ICIs in PWH and uHCC. Our findings encourage the inclusion of patients with well-controlled HIV in prospective clinical trials.

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Abstract Details

Meeting

2024 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Track

Pancreatic Cancer,Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Small Bowel Cancer

Sub Track

Patient-Reported Outcomes and Real-World Evidence

Citation

J Clin Oncol 42, 2024 (suppl 3; abstr 442)

DOI

10.1200/JCO.2024.42.3_suppl.442

Abstract #

442

Poster Bd #

A7

Abstract Disclosures