PMID- 36518086
OWN - NLM
STAT- MEDLINE
DCOM- 20230501
LR  - 20230502
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 12
IP  - 7
DP  - 2023 Apr
TI  - Adverse events as potential predictive factors of therapeutic activity in 
      patients with unresectable hepatocellular carcinoma treated with atezolizumab 
      plus bevacizumab.
PG  - 7772-7783
LID - 10.1002/cam4.5535 [doi]
AB  - AIM: To investigate the possible correlation between the development of adverse 
      events (AEs) and prognosis in patients with unresectable hepatocellular carcinoma 
      (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev). METHODS: A total of 
      286 patients with unresectable HCC treated with Atez/Bev as first-line systematic 
      therapy were included. RESULTS: Regarding treatment-related AEs, decreased 
      appetite of any grade, proteinuria of any grade, and fatigue of any grade were 
      found with a frequency of >/=20%. Multivariate analysis adjusted for immune-related 
      liver injury, immune-related endocrine dysfunction, proteinuria, fatigue, 
      decreased appetite, hypertension, sex, age, Eastern Cooperative Oncology Group 
      performance status, HCC etiology, HCC stage, Child-Pugh score, and alpha-fetoprotein 
      showed that hypertension of any grade (hazard ratio [HR], 0.527; 95% confidence 
      interval [CI], 0.326-0.854; p = 0.009) and alpha-fetoprotein >/=100 ng/ml (HR, 1.642; 
      95% CI, 1.111-2.427; p = 0.013) were independently associated with 
      progression-free survival. Multivariate analysis adjusted for the same AEs showed 
      that fatigue (HR, 2.354; 95% CI, 1.299-4.510; p = 0.010) was independently 
      associated with overall survival. Median progression-free survival was 6.5 months 
      (95% CI, 5.2-8.1) in patients without hypertension of any grade and 12.6 months 
      (95% CI, 6.7-not available) in patients with hypertension of any grade 
      (p = 0.035). The overall survival was significantly shorter in patients in whom 
      treatment-related fatigue of any grade was observed (p < 0.001). Regarding 
      response rates, the disease control rate of patients who developed 
      treatment-related hypertension (94.2%) was significantly higher than those who 
      did not (79.1%) (p = 0.009). CONCLUSIONS: Treatment-related hypertension is 
      associated with good outcomes in patients with HCC treated with Atez/Bev.
CI  - (c) 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Tada, Toshifumi
AU  - Tada T
AUID- ORCID: 0000-0002-0976-6761
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Hyogo Medical University, Nishinomiya, Japan.
AD  - Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, 
      Japan.
FAU - Kumada, Takashi
AU  - Kumada T
AD  - Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
FAU - Hiraoka, Atsushi
AU  - Hiraoka A
AUID- ORCID: 0000-0003-1989-0480
AD  - Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
FAU - Hirooka, Masashi
AU  - Hirooka M
AD  - Department of Gastroenterology and Metabology, Ehime University Graduate School 
      of Medicine, Ehime, Japan.
FAU - Kariyama, Kazuya
AU  - Kariyama K
AUID- ORCID: 0000-0003-3996-7502
AD  - Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
FAU - Tani, Joji
AU  - Tani J
AD  - Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.
FAU - Atsukawa, Masanori
AU  - Atsukawa M
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Takaguchi, Koichi
AU  - Takaguchi K
AD  - Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
FAU - Itobayashi, Ei
AU  - Itobayashi E
AD  - Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
FAU - Fukunishi, Shinya
AU  - Fukunishi S
AD  - Department of Gastroenterology, Osaka Medical and Pharmaceutical University, 
      Osaka, Japan.
FAU - Tsuji, Kunihiko
AU  - Tsuji K
AD  - Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
FAU - Ishikawa, Toru
AU  - Ishikawa T
AD  - Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
FAU - Tajiri, Kazuto
AU  - Tajiri K
AD  - Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
FAU - Ochi, Hironori
AU  - Ochi H
AD  - Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.
FAU - Yasuda, Satoshi
AU  - Yasuda S
AD  - Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, 
      Japan.
FAU - Toyoda, Hidenori
AU  - Toyoda H
AUID- ORCID: 0000-0002-1652-6168
AD  - Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, 
      Japan.
FAU - Ogawa, Chikara
AU  - Ogawa C
AD  - Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, 
      Japan.
FAU - Nishimura, Takashi
AU  - Nishimura T
AUID- ORCID: 0000-0002-5517-8303
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Hyogo Medical University, Nishinomiya, Japan.
FAU - Hatanaka, Takeshi
AU  - Hatanaka T
AUID- ORCID: 0000-0003-3656-285X
AD  - Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, 
      Japan.
FAU - Kakizaki, Satoru
AU  - Kakizaki S
AD  - Department of Clinical Research, National Hospital Organization Takasaki General 
      Medical Center, Takasaki, Japan.
FAU - Shimada, Noritomo
AU  - Shimada N
AD  - Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, 
      Japan.
FAU - Kawata, Kazuhito
AU  - Kawata K
AD  - Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, 
      Japan.
FAU - Tada, Fujimasa
AU  - Tada F
AD  - Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
FAU - Ohama, Hideko
AU  - Ohama H
AD  - Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
FAU - Nouso, Kazuhiro
AU  - Nouso K
AD  - Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
FAU - Morishita, Asahiro
AU  - Morishita A
AD  - Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.
FAU - Tsutsui, Akemi
AU  - Tsutsui A
AD  - Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
FAU - Nagano, Takuya
AU  - Nagano T
AD  - Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
FAU - Itokawa, Norio
AU  - Itokawa N
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Okubo, Tomomi
AU  - Okubo T
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Arai, Taeang
AU  - Arai T
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Imai, Michitaka
AU  - Imai M
AD  - Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
FAU - Kosaka, Hisashi
AU  - Kosaka H
AD  - Department of Surgery, Kansai Medical University, Osaka, Japan.
FAU - Naganuma, Atsushi
AU  - Naganuma A
AUID- ORCID: 0000-0003-0663-0102
AD  - Department of Gastroenterology, National Hospital Organization Takasaki General 
      Medical Center, Takasaki, Japan.
FAU - Koizumi, Yohei
AU  - Koizumi Y
AD  - Department of Gastroenterology and Metabology, Ehime University Graduate School 
      of Medicine, Ehime, Japan.
FAU - Nakamura, Shinichiro
AU  - Nakamura S
AD  - Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, 
      Japan.
FAU - Kaibori, Masaki
AU  - Kaibori M
AD  - Department of Surgery, Kansai Medical University, Osaka, Japan.
FAU - Iijima, Hiroko
AU  - Iijima H
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Hyogo Medical University, Nishinomiya, Japan.
FAU - Hiasa, Yoichi
AU  - Hiasa Y
AUID- ORCID: 0000-0003-4117-339X
AD  - Department of Gastroenterology and Metabology, Ehime University Graduate School 
      of Medicine, Ehime, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221214
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 0 (alpha-Fetoproteins)
RN  - 52CMI0WC3Y (atezolizumab)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Hepatocellular/drug therapy
MH  - Bevacizumab/adverse effects
MH  - alpha-Fetoproteins
MH  - *Liver Neoplasms/drug therapy
MH  - Fatigue/chemically induced
MH  - *Hypertension/chemically induced
MH  - Proteinuria
PMC - PMC10134356
OTO - NOTNLM
OT  - adverse event
OT  - atezolizumab plus bevacizumab
OT  - hepatocellular carcinoma
OT  - survival
COIS- Toshifumi Tada (tadat0627@gmail.com): lecture fees from AbbVie and Eisai. Atsushi 
      Hiraoka (hirage@m.ehime-u.ac.jp): lecture fees from Bayer, Eisai, Eli Lilly, and 
      Otsuka. Takashi Kumada (takashi.kumada@gmail.com): lecture fees from Eisai. 
      Hidenori Toyoda (hmtoyoda@spice.ocn.ne.jp): lecture fees from AbbVie, Bayer, 
      Eisai, Gilead, and Terumo. Takeshi Hatanaka (hatanaka@qk9.so-net.ne.jp): lecture 
      fees from Eisai. None of the other authors have potential conflicts of interest 
      to declare.
EDAT- 2022/12/16 06:00
MHDA- 2023/05/01 06:42
PMCR- 2022/12/14
CRDT- 2022/12/15 02:02
PHST- 2022/11/22 00:00 [revised]
PHST- 2022/08/04 00:00 [received]
PHST- 2022/11/28 00:00 [accepted]
PHST- 2023/05/01 06:42 [medline]
PHST- 2022/12/16 06:00 [pubmed]
PHST- 2022/12/15 02:02 [entrez]
PHST- 2022/12/14 00:00 [pmc-release]
AID - CAM45535 [pii]
AID - 10.1002/cam4.5535 [doi]
PST - ppublish
SO  - Cancer Med. 2023 Apr;12(7):7772-7783. doi: 10.1002/cam4.5535. Epub 2022 Dec 14.