Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab

Mara Persano; Margherita Rimini; Toshifumi Tada; Goki Suda; Shigeo Shimose; Masatoshi Kudo; Federico Rossari; Changhoon Yoo; Jaekyung Cheon; Fabian Finkelmeier; Ho Yeong Lim; José Presa; Gianluca Masi; Francesca Bergamo; Elisabeth Amadeo; Francesco Vitiello; Takashi Kumada; Naoya Sakamoto; Hideki Iwamoto; Tomoko Aoki; Hong Jae Chon; Vera Himmelsbach; Massimo Alberto Iavarone; Giuseppe Cabibbo; Margarida Montes; Francesco Giuseppe Foschi; Caterina Vivaldi; Caterina Soldà; Takuya Sho; Takashi Niizeki; Naoshi Nishida; Christoph Steup; Mariangela Bruccoleri; Masashi Hirooka; Kazuya Kariyama; Joji Tani; Masanori Atsukawa; Koichi Takaguchi; Ei Itobayashi; Shinya Fukunishi; Kunihiko Tsuji; Toru Ishikawa; Kazuto Tajiri; Hironori Ochi; Satoshi Yasuda; Hidenori Toyoda; Chikara Ogawa; Takashi Nishimura; Takeshi Hatanaka; Satoru Kakizaki; Noritomo Shimada; Kazuhito Kawata; Atsushi Hiraoka; Fujimasa Tada; Hideko Ohama; Kazuhiro Nouso; Asahiro Morishita; Akemi Tsutsui; Takuya Nagano; Norio Itokawa; Tomomi Okubo; Michitaka Imai; Hisashi Kosaka; Atsushi Naganuma; Yohei Koizumi; Shinichiro Nakamura; Masaki Kaibori; Hiroko Iijima; Yoichi Hiasa; Silvia Foti; Silvia Camera; Fabio Piscaglia; Mario Scartozzi; Stefano Cascinu; Andrea Casadei-Gardini

doi:10.1007/s11523-024-01061-0

Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab

Mara Persano^*, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Federico Rossari, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko AokiHong Jae Chon, Vera Himmelsbach, Massimo Alberto Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Caterina Soldà, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Mariangela Bruccoleri, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Silvia Foti, Silvia Camera, Fabio Piscaglia, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini

^*Corresponding author for this work

Internal Medicine （3）

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

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Abstract

Background: In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors. Objective: This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting. Patients and methods: The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea). Results: Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13–0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24–0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43–0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38–0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65–0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52–0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64–0.98; p = 0.03) as independent prognostic factors for progression-free survival. Conclusions: As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab.

Original language	English
Pages (from-to)	645-659
Number of pages	15
Journal	Targeted Oncology
Volume	19
Issue number	4
DOIs	https://doi.org/10.1007/s11523-024-01061-0
State	Published - 2024/07

ASJC Scopus subject areas

Oncology
Cancer Research
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s11523-024-01061-0

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Persano, M., Rimini, M., Tada, T., Suda, G., Shimose, S., Kudo, M., Rossari, F., Yoo, C., Cheon, J., Finkelmeier, F., Lim, H. Y., Presa, J., Masi, G., Bergamo, F., Amadeo, E., Vitiello, F., Kumada, T., Sakamoto, N., Iwamoto, H., ... Casadei-Gardini, A. (2024). Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab. Targeted Oncology, 19(4), 645-659. https://doi.org/10.1007/s11523-024-01061-0

@article{8768a9edaaed4670b38d8877d4554a4b,

title = "Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab",

abstract = "Background: In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors. Objective: This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting. Patients and methods: The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea). Results: Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13–0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24–0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43–0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38–0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65–0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52–0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64–0.98; p = 0.03) as independent prognostic factors for progression-free survival. Conclusions: As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab.",

author = "Mara Persano and Margherita Rimini and Toshifumi Tada and Goki Suda and Shigeo Shimose and Masatoshi Kudo and Federico Rossari and Changhoon Yoo and Jaekyung Cheon and Fabian Finkelmeier and Lim, {Ho Yeong} and Jos{\'e} Presa and Gianluca Masi and Francesca Bergamo and Elisabeth Amadeo and Francesco Vitiello and Takashi Kumada and Naoya Sakamoto and Hideki Iwamoto and Tomoko Aoki and Chon, {Hong Jae} and Vera Himmelsbach and Iavarone, {Massimo Alberto} and Giuseppe Cabibbo and Margarida Montes and Foschi, {Francesco Giuseppe} and Caterina Vivaldi and Caterina Sold{\`a} and Takuya Sho and Takashi Niizeki and Naoshi Nishida and Christoph Steup and Mariangela Bruccoleri and Masashi Hirooka and Kazuya Kariyama and Joji Tani and Masanori Atsukawa and Koichi Takaguchi and Ei Itobayashi and Shinya Fukunishi and Kunihiko Tsuji and Toru Ishikawa and Kazuto Tajiri and Hironori Ochi and Satoshi Yasuda and Hidenori Toyoda and Chikara Ogawa and Takashi Nishimura and Takeshi Hatanaka and Satoru Kakizaki and Noritomo Shimada and Kazuhito Kawata and Atsushi Hiraoka and Fujimasa Tada and Hideko Ohama and Kazuhiro Nouso and Asahiro Morishita and Akemi Tsutsui and Takuya Nagano and Norio Itokawa and Tomomi Okubo and Michitaka Imai and Hisashi Kosaka and Atsushi Naganuma and Yohei Koizumi and Shinichiro Nakamura and Masaki Kaibori and Hiroko Iijima and Yoichi Hiasa and Silvia Foti and Silvia Camera and Fabio Piscaglia and Mario Scartozzi and Stefano Cascinu and Andrea Casadei-Gardini",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jul,

doi = "10.1007/s11523-024-01061-0",

language = "英語",

volume = "19",

pages = "645--659",

journal = "Targeted Oncology",

issn = "1776-2596",

publisher = "Springer Paris",

number = "4",

}

Persano, M, Rimini, M, Tada, T, Suda, G, Shimose, S, Kudo, M, Rossari, F, Yoo, C, Cheon, J, Finkelmeier, F, Lim, HY, Presa, J, Masi, G, Bergamo, F, Amadeo, E, Vitiello, F, Kumada, T, Sakamoto, N, Iwamoto, H, Aoki, T, Chon, HJ, Himmelsbach, V, Iavarone, MA, Cabibbo, G, Montes, M, Foschi, FG, Vivaldi, C, Soldà, C, Sho, T, Niizeki, T, Nishida, N, Steup, C, Bruccoleri, M, Hirooka, M, Kariyama, K, Tani, J, Atsukawa, M, Takaguchi, K, Itobayashi, E, Fukunishi, S, Tsuji, K, Ishikawa, T, Tajiri, K, Ochi, H, Yasuda, S, Toyoda, H, Ogawa, C, Nishimura, T, Hatanaka, T, Kakizaki, S, Shimada, N, Kawata, K, Hiraoka, A, Tada, F, Ohama, H, Nouso, K, Morishita, A, Tsutsui, A, Nagano, T, Itokawa, N, Okubo, T, Imai, M, Kosaka, H, Naganuma, A, Koizumi, Y, Nakamura, S, Kaibori, M, Iijima, H, Hiasa, Y, Foti, S, Camera, S, Piscaglia, F, Scartozzi, M, Cascinu, S & Casadei-Gardini, A 2024, 'Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab', Targeted Oncology, vol. 19, no. 4, pp. 645-659. https://doi.org/10.1007/s11523-024-01061-0

TY - JOUR

T1 - Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab

AU - Persano, Mara

AU - Rimini, Margherita

AU - Tada, Toshifumi

AU - Suda, Goki

AU - Shimose, Shigeo

AU - Kudo, Masatoshi

AU - Rossari, Federico

AU - Yoo, Changhoon

AU - Cheon, Jaekyung

AU - Finkelmeier, Fabian

AU - Lim, Ho Yeong

AU - Presa, José

AU - Masi, Gianluca

AU - Bergamo, Francesca

AU - Amadeo, Elisabeth

AU - Vitiello, Francesco

AU - Kumada, Takashi

AU - Sakamoto, Naoya

AU - Iwamoto, Hideki

AU - Aoki, Tomoko

AU - Chon, Hong Jae

AU - Himmelsbach, Vera

AU - Iavarone, Massimo Alberto

AU - Cabibbo, Giuseppe

AU - Montes, Margarida

AU - Foschi, Francesco Giuseppe

AU - Vivaldi, Caterina

AU - Soldà, Caterina

AU - Sho, Takuya

AU - Niizeki, Takashi

AU - Nishida, Naoshi

AU - Steup, Christoph

AU - Bruccoleri, Mariangela

AU - Hirooka, Masashi

AU - Kariyama, Kazuya

AU - Tani, Joji

AU - Atsukawa, Masanori

AU - Takaguchi, Koichi

AU - Itobayashi, Ei

AU - Fukunishi, Shinya

AU - Tsuji, Kunihiko

AU - Ishikawa, Toru

AU - Tajiri, Kazuto

AU - Ochi, Hironori

AU - Yasuda, Satoshi

AU - Toyoda, Hidenori

AU - Ogawa, Chikara

AU - Nishimura, Takashi

AU - Hatanaka, Takeshi

AU - Kakizaki, Satoru

AU - Shimada, Noritomo

AU - Kawata, Kazuhito

AU - Hiraoka, Atsushi

AU - Tada, Fujimasa

AU - Ohama, Hideko

AU - Nouso, Kazuhiro

AU - Morishita, Asahiro

AU - Tsutsui, Akemi

AU - Nagano, Takuya

AU - Itokawa, Norio

AU - Okubo, Tomomi

AU - Imai, Michitaka

AU - Kosaka, Hisashi

AU - Naganuma, Atsushi

AU - Koizumi, Yohei

AU - Nakamura, Shinichiro

AU - Kaibori, Masaki

AU - Iijima, Hiroko

AU - Hiasa, Yoichi

AU - Foti, Silvia

AU - Camera, Silvia

AU - Piscaglia, Fabio

AU - Scartozzi, Mario

AU - Cascinu, Stefano

AU - Casadei-Gardini, Andrea

PY - 2024/7

Y1 - 2024/7

N2 - Background: In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors. Objective: This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting. Patients and methods: The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea). Results: Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13–0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24–0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43–0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38–0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65–0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52–0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64–0.98; p = 0.03) as independent prognostic factors for progression-free survival. Conclusions: As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab.

AB - Background: In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors. Objective: This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting. Patients and methods: The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea). Results: Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13–0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24–0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43–0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38–0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65–0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52–0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64–0.98; p = 0.03) as independent prognostic factors for progression-free survival. Conclusions: As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab.

UR - http://www.scopus.com/inward/record.url?scp=85191859279&partnerID=8YFLogxK

U2 - 10.1007/s11523-024-01061-0

DO - 10.1007/s11523-024-01061-0

M3 - 学術論文

C2 - 38689194

AN - SCOPUS:85191859279

SN - 1776-2596

VL - 19

SP - 645

EP - 659

JO - Targeted Oncology

JF - Targeted Oncology

IS - 4

ER -

Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab

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