Patients (pts) with advanced hepatocellular carcinoma (HCC) with long-term response to immune checkpoint inhibitor (ICI) therapy

Long-term responders to ICI occur in advanced HCC pts; though little is known about ultimate outcomes and treatment trajectory. A clinical knowledge gap exists for long-term disease control patients, in particular, the proportion of those who remain disease free indefinitely, who stop therapy, and those with disease escape who may be rescued with loco-regional therapy, metastastectomy, and/or are rechallenged with ICI therapy.

This was a single-center, IRB-approved, retrospective study of histologically confirmed HCC pts treated with an ICI (anti-PD-1/PD-L1) monotherapy or in combination at Memorial Sloan Kettering Cancer Center from 2012-2022. The primary objective was to describe the treatment trajectory and outcomes in pts with durable disease control with anti-PD1 based therapy. Long-term disease control/response was defined as ≥1 year of disease control (stable disease or response on imaging as per treating physician) from the start of ICI.

Of 253 HCC pts who received ICI, 34 pts (13%) met criteria for long-term disease control. Pts were median age 70 years (range 17-87), mostly male (25, 71%), with viral (65%) vs. non-viral (35%) etiology. All had advanced HCC [8 (76%) BCLC C and 26 (24%) BCLC-B] with Child-Pugh score A in 97%. Of the 34 pts, 65% received single agent PD-L1/1 inhibitor. Of the other 35% who received ICI in combination: 6 were treated with anti-VEGF antibodies, 3 with tyrosine kinase inhibitor, 2 with anti-CTLA-4, and 1 with anti-LAG-3. The median follow-up from start of ICI was 34.8 months. At the data lock, N = 6 (18%) continued ICI (median duration of treatment 23.6 months, range 19.6 – 34.3+ months). Of those who discontinued ICI (N = 28, 82%), reasons for discontinuation were disease progression (16), immune-related AEs (5), death from other cause (5) or patient-physician decision (2). Of the 12 pts who stopped ICI for reasons other than disease progression, 5 pts died from other causes without evidence of HCC progression. Of the 7-remaining pts, 4 pts had no evidence of disease recurrence at median follow-up of 33 months from ICI discontinuation; and 1 pt resumed anti-PD-1 therapy after definitive management of a second malignancy and remains with disease control. Of the 2 pts with disease recurrence, 1 had lung only recurrence 23.2 months after ICI discontinuation and upon ICI rechallenge attained disease response followed by metastastectomy; 1 had liver only recurrence treated with TACE 2.7 months after ICI discontinuation, and is without recurrence > 12 months post-TACE.

Durable disease control with anti-PD1 therapy is infrequent. After treatment discontinuation, sustained disease stability may be observed, and/or, in cases of oligometastatic escape local therapy may be employed to patient benefit. Considering the limited cohort of such pts, this effort needs to be expanded among different sites and institutions.

The authors.

Has not received any funding.

J. Shia: Advisory / Consultancy: Paige AI. E. O'Reilly: Advisory / Consultancy: Boehringer Ingelheim, BioNTech, Ipsen, Merck, Novartis, AstraZeneca, BioSapien, Astellas, Thetis, Autem, Novocure, Neogene, BMS, Tempus, Fibrogen, Merus, Agios (spouse), Genentech-Roche (spouse), Eisai (spouse); Research grant / Funding (institution): Genentech/Roche, BioNTech, AstraZeneca, Arcus, Elicio, Parker Institute, NIH/NCI, Pertzye; Spouse / Financial dependant: Agios, Genentech-Roche, Eisai; Non-remunerated activity/iesA: BioSapien, Thetis. G. Abou-Alfa: Advisory / Consultancy: Astellas, Astra Zeneca, Autem, Berry Genomics, BioNtech, Boehringer Ingelheim, BMS, Eisai, Exelixis, Fibriogen, Genentech/Roche, Helio, Incyte, Ipsen, Merck, Merus, Neogene, Newbridge, Novartis, QED, Servier, Tempus, Thetis, Vector, Yiviva; Research grant / Funding (self): Agenus, Arcus, Astra Zeneca, BioNtech, BMS, Elicio, Genentech/Roche, Helsinn, Parker Institute, Pertzye, Puma, QED, Yiviva. J. Harding: Honoraria (self): HCC Connect, OncLive; Advisory / Consultancy: Adaptimmune, AstraZeneca, Bristol Myers Squibb, Exelexis, Elevar, Eisai, Genoscience (uncompensated), Hepion, Imvax, Merck (DSMB) Medivir, QED, Tyra, Zymeworks (uncompensated); Research grant / Funding (institution): Bristol Myers Squibb, Boehringer Ingelheim, CytomX, Debiopharm, Eli Lilly, Genoscience, Incyte, Loxo @ Lilly, Novartis, Polaris, Pfizer, Zymeworks, Yiviva. All other authors have declared no conflicts of interest.