Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma

Mathew Vithayathil; Antonio D'Alessio; Claudia A.M. Fulgenzi; Naoshi Nishida; Martin Schönlein; Johann von Felden; Kornelius Schulze; Henning Wege; Anwaar Saeed; Brooke Wietharn; Hannah Hildebrand; Linda Wu; Celina Ang; Thomas U. Marron; Arndt Weinmann; Peter R. Galle; Dominik Bettinger; Bertram Bengsch; Arndt Vogel; Lorenz Balcar; Bernhard Scheiner; Pei Chang Lee; Yi Hsiang Huang; Suneetha Amara; Mahvish Muzaffar; Abdul Rafeh Naqash; Antonella Cammarota; Nicola Personeni; Tiziana Pressiani; Matthias Pinter; Alessio Cortellini; Masatoshi Kudo; Lorenza Rimassa; David J. Pinato; Rohini Sharma

doi:10.1111/liv.15405

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma

Mathew Vithayathil, Antonio D'Alessio, Claudia A.M. Fulgenzi, Naoshi Nishida, Martin Schönlein, Johann von Felden, Kornelius Schulze, Henning Wege, Anwaar Saeed, Brooke Wietharn, Hannah Hildebrand, Linda Wu, Celina Ang, Thomas U. Marron, Arndt Weinmann, Peter R. Galle, Dominik Bettinger, Bertram Bengsch, Arndt Vogel, Lorenz BalcarBernhard Scheiner, Pei Chang Lee, Yi Hsiang Huang, Suneetha Amara, Mahvish Muzaffar, Abdul Rafeh Naqash, Antonella Cammarota, Nicola Personeni, Tiziana Pressiani, Matthias Pinter, Alessio Cortellini, Masatoshi Kudo, Lorenza Rimassa, David J. Pinato, Rohini Sharma

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

18 Scopus citations

Abstract

Background and Aims: Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. Methods: 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age < 65 years) age patients. Treatment-related adverse events (trAEs) were evaluated. Results: The elderly (n = 116) had higher rates of non-alcoholic fatty liver disease (19.8% vs. 2.7%; p <.001), presenting with smaller tumours (6.2 cm vs 7.9 cm, p =.02) with less portal vein thrombosis (31.9 vs. 54.7%, p =.002), with fewer patients presenting with BCLC-C stage disease (50.9 vs. 74.3%, p =.002). There was no significant difference in OS (median 14.9 vs. 15.1 months; HR 1.15, 95% CI 0.65–2.02 p =.63) and PFS (median 7.1 vs. 5.5 months; HR 1.11, 95% CI 0.54–1.92; p =.72) between older age and younger age. Older patients had similar ORR (27.6% vs. 20.0%; p =.27) and DCR (77.5% vs. 66.1%; p =.11) compared to younger patients. Atezolizumab-related (40.5% vs. 48.0%; p =.31) and bevacizumab-related (44.8% vs. 41.3%; p =.63) trAEs were comparable between groups. Rates of grade ≥3 trAEs and toxicity-related treatment discontinuation were similar between older and younger age patients. Patients 75 years and older had similar survival and safety outcomes compared to younger patients. Conclusions: Atezolizumab and bevacizumab therapy is associated with comparable efficacy and tolerability in older age patients with unresectable HCC.

Original language	English
Pages (from-to)	2538-2547
Number of pages	10
Journal	Liver International
Volume	42
Issue number	11
DOIs	https://doi.org/10.1111/liv.15405
State	Published - Nov 2022

Keywords

anti-programmed death-ligand
anti-vascular endothelial growth factor
checkpoint inhibitor
cirrhosis
immunotherapy

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10.1111/liv.15405

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Vithayathil, M., D'Alessio, A., Fulgenzi, C. A. M., Nishida, N., Schönlein, M., von Felden, J., Schulze, K., Wege, H., Saeed, A., Wietharn, B., Hildebrand, H., Wu, L., Ang, C., Marron, T. U., Weinmann, A., Galle, P. R., Bettinger, D., Bengsch, B., Vogel, A., ... Sharma, R. (2022). Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Liver International, 42(11), 2538-2547. https://doi.org/10.1111/liv.15405

@article{72e9d6c254634bb593c3685758b12f53,

title = "Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma",

abstract = "Background and Aims: Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. Methods: 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age < 65 years) age patients. Treatment-related adverse events (trAEs) were evaluated. Results: The elderly (n = 116) had higher rates of non-alcoholic fatty liver disease (19.8% vs. 2.7%; p <.001), presenting with smaller tumours (6.2 cm vs 7.9 cm, p =.02) with less portal vein thrombosis (31.9 vs. 54.7%, p =.002), with fewer patients presenting with BCLC-C stage disease (50.9 vs. 74.3%, p =.002). There was no significant difference in OS (median 14.9 vs. 15.1 months; HR 1.15, 95% CI 0.65–2.02 p =.63) and PFS (median 7.1 vs. 5.5 months; HR 1.11, 95% CI 0.54–1.92; p =.72) between older age and younger age. Older patients had similar ORR (27.6% vs. 20.0%; p =.27) and DCR (77.5% vs. 66.1%; p =.11) compared to younger patients. Atezolizumab-related (40.5% vs. 48.0%; p =.31) and bevacizumab-related (44.8% vs. 41.3%; p =.63) trAEs were comparable between groups. Rates of grade ≥3 trAEs and toxicity-related treatment discontinuation were similar between older and younger age patients. Patients 75 years and older had similar survival and safety outcomes compared to younger patients. Conclusions: Atezolizumab and bevacizumab therapy is associated with comparable efficacy and tolerability in older age patients with unresectable HCC.",

keywords = "anti-programmed death-ligand, anti-vascular endothelial growth factor, checkpoint inhibitor, cirrhosis, immunotherapy",

author = "Mathew Vithayathil and Antonio D'Alessio and Fulgenzi, {Claudia A.M.} and Naoshi Nishida and Martin Sch{\"o}nlein and {von Felden}, Johann and Kornelius Schulze and Henning Wege and Anwaar Saeed and Brooke Wietharn and Hannah Hildebrand and Linda Wu and Celina Ang and Marron, {Thomas U.} and Arndt Weinmann and Galle, {Peter R.} and Dominik Bettinger and Bertram Bengsch and Arndt Vogel and Lorenz Balcar and Bernhard Scheiner and Lee, {Pei Chang} and Huang, {Yi Hsiang} and Suneetha Amara and Mahvish Muzaffar and Naqash, {Abdul Rafeh} and Antonella Cammarota and Nicola Personeni and Tiziana Pressiani and Matthias Pinter and Alessio Cortellini and Masatoshi Kudo and Lorenza Rimassa and Pinato, {David J.} and Rohini Sharma",

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

year = "2022",

month = nov,

doi = "10.1111/liv.15405",

language = "English",

volume = "42",

pages = "2538--2547",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "11",

}

Vithayathil, M, D'Alessio, A, Fulgenzi, CAM, Nishida, N, Schönlein, M, von Felden, J, Schulze, K, Wege, H, Saeed, A, Wietharn, B, Hildebrand, H, Wu, L, Ang, C , Marron, TU, Weinmann, A, Galle, PR, Bettinger, D, Bengsch, B, Vogel, A, Balcar, L, Scheiner, B, Lee, PC, Huang, YH, Amara, S, Muzaffar, M, Naqash, AR, Cammarota, A, Personeni, N, Pressiani, T, Pinter, M, Cortellini, A, Kudo, M, Rimassa, L, Pinato, DJ & Sharma, R 2022, 'Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma', Liver International, vol. 42, no. 11, pp. 2538-2547. https://doi.org/10.1111/liv.15405

TY - JOUR

T1 - Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma

AU - Vithayathil, Mathew

AU - D'Alessio, Antonio

AU - Fulgenzi, Claudia A.M.

AU - Nishida, Naoshi

AU - Schönlein, Martin

AU - von Felden, Johann

AU - Schulze, Kornelius

AU - Wege, Henning

AU - Saeed, Anwaar

AU - Wietharn, Brooke

AU - Hildebrand, Hannah

AU - Wu, Linda

AU - Ang, Celina

AU - Marron, Thomas U.

AU - Weinmann, Arndt

AU - Galle, Peter R.

AU - Bettinger, Dominik

AU - Bengsch, Bertram

AU - Vogel, Arndt

AU - Balcar, Lorenz

AU - Scheiner, Bernhard

AU - Lee, Pei Chang

AU - Huang, Yi Hsiang

AU - Amara, Suneetha

AU - Muzaffar, Mahvish

AU - Naqash, Abdul Rafeh

AU - Cammarota, Antonella

AU - Personeni, Nicola

AU - Pressiani, Tiziana

AU - Pinter, Matthias

AU - Cortellini, Alessio

AU - Kudo, Masatoshi

AU - Rimassa, Lorenza

AU - Pinato, David J.

AU - Sharma, Rohini

PY - 2022/11

Y1 - 2022/11

N2 - Background and Aims: Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. Methods: 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age < 65 years) age patients. Treatment-related adverse events (trAEs) were evaluated. Results: The elderly (n = 116) had higher rates of non-alcoholic fatty liver disease (19.8% vs. 2.7%; p <.001), presenting with smaller tumours (6.2 cm vs 7.9 cm, p =.02) with less portal vein thrombosis (31.9 vs. 54.7%, p =.002), with fewer patients presenting with BCLC-C stage disease (50.9 vs. 74.3%, p =.002). There was no significant difference in OS (median 14.9 vs. 15.1 months; HR 1.15, 95% CI 0.65–2.02 p =.63) and PFS (median 7.1 vs. 5.5 months; HR 1.11, 95% CI 0.54–1.92; p =.72) between older age and younger age. Older patients had similar ORR (27.6% vs. 20.0%; p =.27) and DCR (77.5% vs. 66.1%; p =.11) compared to younger patients. Atezolizumab-related (40.5% vs. 48.0%; p =.31) and bevacizumab-related (44.8% vs. 41.3%; p =.63) trAEs were comparable between groups. Rates of grade ≥3 trAEs and toxicity-related treatment discontinuation were similar between older and younger age patients. Patients 75 years and older had similar survival and safety outcomes compared to younger patients. Conclusions: Atezolizumab and bevacizumab therapy is associated with comparable efficacy and tolerability in older age patients with unresectable HCC.

AB - Background and Aims: Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. Methods: 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age < 65 years) age patients. Treatment-related adverse events (trAEs) were evaluated. Results: The elderly (n = 116) had higher rates of non-alcoholic fatty liver disease (19.8% vs. 2.7%; p <.001), presenting with smaller tumours (6.2 cm vs 7.9 cm, p =.02) with less portal vein thrombosis (31.9 vs. 54.7%, p =.002), with fewer patients presenting with BCLC-C stage disease (50.9 vs. 74.3%, p =.002). There was no significant difference in OS (median 14.9 vs. 15.1 months; HR 1.15, 95% CI 0.65–2.02 p =.63) and PFS (median 7.1 vs. 5.5 months; HR 1.11, 95% CI 0.54–1.92; p =.72) between older age and younger age. Older patients had similar ORR (27.6% vs. 20.0%; p =.27) and DCR (77.5% vs. 66.1%; p =.11) compared to younger patients. Atezolizumab-related (40.5% vs. 48.0%; p =.31) and bevacizumab-related (44.8% vs. 41.3%; p =.63) trAEs were comparable between groups. Rates of grade ≥3 trAEs and toxicity-related treatment discontinuation were similar between older and younger age patients. Patients 75 years and older had similar survival and safety outcomes compared to younger patients. Conclusions: Atezolizumab and bevacizumab therapy is associated with comparable efficacy and tolerability in older age patients with unresectable HCC.

KW - anti-programmed death-ligand

KW - anti-vascular endothelial growth factor

KW - checkpoint inhibitor

KW - cirrhosis

KW - immunotherapy

UR - http://www.scopus.com/inward/record.url?scp=85137373130&partnerID=8YFLogxK

U2 - 10.1111/liv.15405

DO - 10.1111/liv.15405

M3 - Article

C2 - 35986902

AN - SCOPUS:85137373130

SN - 1478-3223

VL - 42

SP - 2538

EP - 2547

JO - Liver International

JF - Liver International

IS - 11

ER -

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma

Abstract

Keywords

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