Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Thomas Talbot; Antonio D'Alessio; Matthias Pinter; Lorenz Balcar; Bernhard Scheiner; Thomas U. Marron; Tomi Jun; Sirish Dharmapuri; Celina Ang; Anwaar Saeed; Hannah Hildebrand; Mahvish Muzaffar; Claudia A.M. Fulgenzi; Suneetha Amara; Abdul Rafeh Naqash; Anuhya Gampa; Anjana Pillai; Yinghong Wang; Uqba Khan; Pei Chang Lee; Yi Hsiang Huang; Bertram Bengsch; Dominik Bettinger; Yehia I. Mohamed; Ahmed Kaseb; Tiziana Pressiani; Nicola Personeni; Lorenza Rimassa; Naoshi Nishida; Masatoshi Kudo; Arndt Weinmann; Peter R. Galle; Ambreen Muhammed; Alessio Cortellini; Arndt Vogel; David J. Pinato

doi:10.1111/liv.15502

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Thomas Talbot, Antonio D'Alessio, Matthias Pinter, Lorenz Balcar, Bernhard Scheiner, Thomas U. Marron, Tomi Jun, Sirish Dharmapuri, Celina Ang, Anwaar Saeed, Hannah Hildebrand, Mahvish Muzaffar, Claudia A.M. Fulgenzi, Suneetha Amara, Abdul Rafeh Naqash, Anuhya Gampa, Anjana Pillai, Yinghong Wang, Uqba Khan, Pei Chang LeeYi Hsiang Huang, Bertram Bengsch, Dominik Bettinger, Yehia I. Mohamed, Ahmed Kaseb, Tiziana Pressiani, Nicola Personeni, Lorenza Rimassa, Naoshi Nishida, Masatoshi Kudo, Arndt Weinmann, Peter R. Galle, Ambreen Muhammed, Alessio Cortellini, Arndt Vogel, David J. Pinato

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Background and Aims: Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies. Methods: We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI). Results: Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p =.0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p =.0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p <.0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p <.0001) as predictors of prolonged PPS versus no anticancer therapy. Conclusions: ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.

Original language	English (US)
Pages (from-to)	695-707
Number of pages	13
Journal	Liver International
Volume	43
Issue number	3
DOIs	https://doi.org/10.1111/liv.15502
State	Published - Mar 2023

ASJC Scopus subject areas

Hepatology

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Talbot, T., D'Alessio, A., Pinter, M., Balcar, L., Scheiner, B., Marron, T. U., Jun, T., Dharmapuri, S., Ang, C., Saeed, A., Hildebrand, H., Muzaffar, M., Fulgenzi, C. A. M., Amara, S., Naqash, A. R., Gampa, A., Pillai, A., Wang, Y., Khan, U., ... Pinato, D. J. (2023). Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study. Liver International, 43(3), 695-707. https://doi.org/10.1111/liv.15502

Talbot, T, D'Alessio, A, Pinter, M, Balcar, L, Scheiner, B, Marron, TU, Jun, T, Dharmapuri, S, Ang, C, Saeed, A, Hildebrand, H, Muzaffar, M, Fulgenzi, CAM, Amara, S, Naqash, AR, Gampa, A, Pillai, A, Wang, Y, Khan, U, Lee, PC, Huang, YH, Bengsch, B, Bettinger, D, Mohamed, YI , Kaseb, A, Pressiani, T, Personeni, N, Rimassa, L, Nishida, N, Kudo, M, Weinmann, A, Galle, PR, Muhammed, A, Cortellini, A, Vogel, A & Pinato, DJ 2023, 'Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study', Liver International, vol. 43, no. 3, pp. 695-707. https://doi.org/10.1111/liv.15502

@article{6c4507e67c8448ddb224521d8952fcc1,

title = "Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study",

abstract = "Background and Aims: Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies. Methods: We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI). Results: Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p =.0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p =.0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p <.0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p <.0001) as predictors of prolonged PPS versus no anticancer therapy. Conclusions: ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.",

author = "Thomas Talbot and Antonio D'Alessio and Matthias Pinter and Lorenz Balcar and Bernhard Scheiner and Marron, {Thomas U.} and Tomi Jun and Sirish Dharmapuri and Celina Ang and Anwaar Saeed and Hannah Hildebrand and Mahvish Muzaffar and Fulgenzi, {Claudia A.M.} and Suneetha Amara and Naqash, {Abdul Rafeh} and Anuhya Gampa and Anjana Pillai and Yinghong Wang and Uqba Khan and Lee, {Pei Chang} and Huang, {Yi Hsiang} and Bertram Bengsch and Dominik Bettinger and Mohamed, {Yehia I.} and Ahmed Kaseb and Tiziana Pressiani and Nicola Personeni and Lorenza Rimassa and Naoshi Nishida and Masatoshi Kudo and Arndt Weinmann and Galle, {Peter R.} and Ambreen Muhammed and Alessio Cortellini and Arndt Vogel and Pinato, {David J.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Liver International published by John Wiley & Sons Ltd.",

year = "2023",

month = mar,

doi = "10.1111/liv.15502",

language = "English (US)",

volume = "43",

pages = "695--707",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma

T2 - An international observational study

AU - Talbot, Thomas

AU - D'Alessio, Antonio

AU - Pinter, Matthias

AU - Balcar, Lorenz

AU - Scheiner, Bernhard

AU - Marron, Thomas U.

AU - Jun, Tomi

AU - Dharmapuri, Sirish

AU - Ang, Celina

AU - Saeed, Anwaar

AU - Hildebrand, Hannah

AU - Muzaffar, Mahvish

AU - Fulgenzi, Claudia A.M.

AU - Amara, Suneetha

AU - Naqash, Abdul Rafeh

AU - Gampa, Anuhya

AU - Pillai, Anjana

AU - Wang, Yinghong

AU - Khan, Uqba

AU - Lee, Pei Chang

AU - Huang, Yi Hsiang

AU - Bengsch, Bertram

AU - Bettinger, Dominik

AU - Mohamed, Yehia I.

AU - Kaseb, Ahmed

AU - Pressiani, Tiziana

AU - Personeni, Nicola

AU - Rimassa, Lorenza

AU - Nishida, Naoshi

AU - Kudo, Masatoshi

AU - Weinmann, Arndt

AU - Galle, Peter R.

AU - Muhammed, Ambreen

AU - Cortellini, Alessio

AU - Vogel, Arndt

AU - Pinato, David J.

PY - 2023/3

Y1 - 2023/3

N2 - Background and Aims: Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies. Methods: We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI). Results: Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p =.0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p =.0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p <.0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p <.0001) as predictors of prolonged PPS versus no anticancer therapy. Conclusions: ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.

AB - Background and Aims: Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies. Methods: We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI). Results: Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p =.0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p =.0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p <.0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p <.0001) as predictors of prolonged PPS versus no anticancer therapy. Conclusions: ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.

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UR - http://www.scopus.com/inward/citedby.url?scp=85146310425&partnerID=8YFLogxK

U2 - 10.1111/liv.15502

DO - 10.1111/liv.15502

M3 - Article

C2 - 36577703

AN - SCOPUS:85146310425

SN - 1478-3223

VL - 43

SP - 695

EP - 707

JO - Liver International

JF - Liver International

IS - 3

ER -

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

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