Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma

Haber, Philipp K.; Castet, Florian; Torres‐Martín, Miguel; Andreu-Oller, Carmen; Puigvehí, Marc; Maeda, Miho; Radu, Pompilia; Dufour, Jean‐François; Verslype, Chris; Czauderna, Carolin; Marquardt, Jens U.; Galle, Peter R.; Vogel, Arndt; Bathon, Melanie; Meyer, Tim; Labgaa, Ismaïl; Digklia, Antonia; Roberts, Lewis R.; Ali, Mohamed A. Mohamed; Mínguez, Beatriz; Citterio, Davide; Mazzaferro, Vincenzo; Finkelmeier, Fabian; Trojan, Jörg; Özdirik, Burcin; Müller, Tobias; Schmelzle, Moritz; Bejjani, Anthony; Sung, Max W.; Schwartz, Myron; Finn, Richard S.; Thung, Swan N.; Villanueva, Augusto; Sia, Daniela; Llovet, Josep M.

doi:10.1053/j.gastro.2022.09.005

Cited by 69 publications

(55 citation statements)

References 51 publications

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“…In addition, there is a need to identify biomarkers predicting response to single ICI or combinations. Post-hoc analysis of PD-L1 expression did not predict response to single agent ICI s 19 , 113 , while gene signatures are in need of further validation 61 , 62 . Liquid biopsy has emerged as a non-invasive technology for biomarker discovery in HCC 167 .…”

Section: Future Directionsmentioning

confidence: 86%

“…Non-inflamed- cold tumors are characterized by T cell exclusion, and either TP53 mutations (intermediate class) or activation of canonical Wnt signaling through CTNNB1 mutations (excluded class) 6 , 55 . Whether ‘inflamed’ HCCs or other immune-related biomarkers are associated with response to immune checkpoint blockers is currently being investigated 61 , 62 .…”

Section: Molecular Pathogenesismentioning

confidence: 99%

“…In a subset of 37 patients, associations with ORR or overall survival were noted for 7 out of 10 evaluated inflammatory gene signatures 61 . A recent study also identified a gene signature able to predict response to either nivolumab or pembrolizumab 62 . If validated, such emerging biomarkers may be utilized for patient selection in the future.…”

Section: Evidence-based Knowledge For Systemic Therapies In Hccmentioning

confidence: 99%

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Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

et al. 2022

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Section: Future Directionsmentioning

confidence: 86%

Section: Molecular Pathogenesismentioning

confidence: 99%

Section: Evidence-based Knowledge For Systemic Therapies In Hccmentioning

confidence: 99%

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Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

et al. 2022

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“…Unfortunately, several candidate molecular and immunohistochemical biomarkers to identify patients likely to benefit, which are well-known from other cancer entities, showed no predictive capacity or have too low a prevalence in patients with HCC [9,[36][37][38]. Novel biomarkers like circulating tumor cells or composition of the gut microbiota as well as newly identified gene signatures are currently investigated and showed promising initial results in first proof-of-concept studies [10,39,40].…”

Section: Discussionmentioning

confidence: 99%

The prognostic role of early tumor shrinkage in patients with hepatocellular carcinoma undergoing immunotherapy

et al. 2022

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Background Early tumor shrinkage (ETS) has been identified as a promising imaging biomarker for patients undergoing immunotherapy for several cancer entities. This study aimed to validate the potential of ETS as an imaging biomarker for patients undergoing immunotherapy for hepatocellular carcinoma (HCC). Methods We screened all patients with HCC that received immunotherapy as the first or subsequent line of treatment at our tertiary care center between 2016 and 2021. ETS was defined as the reduction in the sum of the sizes of target lesions, between the initial imaging and the first follow-up. The ETS was compared to the radiologic response, according to the modified response evaluation criteria in solid tumors (mRECIST). Furthermore, we evaluated the influence of ETS on overall survival (OS), progression-free survival (PFS), and the alpha-fetoprotein (AFP) response. Results The final analysis included 39 patients with available cross-sectional imaging acquired at the initiation of immunotherapy (baseline) and after 8–14 weeks. The median ETS was 5.4%. ETS was significantly correlated with the response according to mRECIST and with the AFP response. Patients with an ETS ≥10% had significantly longer survival times after the first follow-up, compared to patients with < 10% ETS (15.1 months vs. 4.0 months, p = 0.008). Additionally, patients with both an ETS ≥10% and disease control, according to mRECIST, also had significantly prolonged PFS times after the initial follow-up (23.6 months vs. 2.4 months, p < 0.001). Conclusion ETS was strongly associated with survival outcomes in patients with HCC undergoing immunotherapy. Thus, ETS is a readily assessable imaging biomarker that showed potential for facilitating a timely identification of patients with HCC that might benefit from immunotherapy.

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“…In fact, major efforts in several neoadjuvant trials and studies are already in place to clarify these questions. [80][81][82]…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti‐VEGF/TKI and immunotherapy

et al. 2022

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Hepatocellular carcinoma remains a global health challenge affecting close to 1 million cases yearly. Liver transplantation provides the best long‐term outcomes for those meeting strict criteria. Efforts have been made to expand these criteria, whereas others have attempted downstaging approaches. Although locoregional approaches to downstaging are appealing and have demonstrated efficacy, limitations and challenges exists including poor imaging modality to assess response and appropriate endpoints along the process. Recent advances in systemic treatments including immune checkpoint inhibitors alone or in combination with tyrosine kinase inhibitors have prompted the discussion regarding their role for downstaging disease prior to transplantation. Here, we provide a review of prior locoregional approaches for downstaging, new systemic agents and their role for downstaging, and finally, key and critical considerations of the assessment, endpoints, and optimal designs in clinical trials to address this key question.

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Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma

Cited by 69 publications

References 51 publications

Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

The prognostic role of early tumor shrinkage in patients with hepatocellular carcinoma undergoing immunotherapy

Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti‐VEGF/TKI and immunotherapy

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