Cancer Medicine (Apr 2023)
Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab
- Toshifumi Tada,
- Takashi Kumada,
- Atsushi Hiraoka,
- 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,
- Fujimasa Tada,
- Hideko Ohama,
- Kazuhiro Nouso,
- Asahiro Morishita,
- Akemi Tsutsui,
- Takuya Nagano,
- Norio Itokawa,
- Tomomi Okubo,
- Taeang Arai,
- Michitaka Imai,
- Hisashi Kosaka,
- Atsushi Naganuma,
- Yohei Koizumi,
- Shinichiro Nakamura,
- Masaki Kaibori,
- Hiroko Iijima,
- Yoichi Hiasa
Affiliations
- Toshifumi Tada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Hyogo Medical University Nishinomiya Japan
- Takashi Kumada
- Department of Nursing Gifu Kyoritsu University Ogaki Japan
- Atsushi Hiraoka
- Gastroenterology Center Ehime Prefectural Central Hospital Matsuyama Japan
- Masashi Hirooka
- Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine Ehime Japan
- Kazuya Kariyama
- Department of Gastroenterology Okayama City Hospital Okayama Japan
- Joji Tani
- Department of Gastroenterology and Hepatology Kagawa University Kagawa Japan
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo Japan
- Koichi Takaguchi
- Department of Hepatology Kagawa Prefectural Central Hospital Takamatsu Japan
- Ei Itobayashi
- Department of Gastroenterology Asahi General Hospital Asahi Japan
- Shinya Fukunishi
- Department of Gastroenterology Osaka Medical and Pharmaceutical University Osaka Japan
- Kunihiko Tsuji
- Center of Gastroenterology Teine Keijinkai Hospital Sapporo Japan
- Toru Ishikawa
- Department of Gastroenterology Saiseikai Niigata Hospital Niigata Japan
- Kazuto Tajiri
- Department of Gastroenterology Toyama University Hospital Toyama Japan
- Hironori Ochi
- Hepato‐biliary Center Japanese Red Cross Matsuyama Hospital Matsuyama Japan
- Satoshi Yasuda
- Department of Gastroenterology and Hepatology Ogaki Municipal Hospital Ogaki Japan
- Hidenori Toyoda
- Department of Gastroenterology and Hepatology Ogaki Municipal Hospital Ogaki Japan
- Chikara Ogawa
- Department of Gastroenterology Japanese Red Cross Takamatsu Hospital Takamatsu Japan
- Takashi Nishimura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Hyogo Medical University Nishinomiya Japan
- Takeshi Hatanaka
- Department of Gastroenterology Gunma Saiseikai Maebashi Hospital Maebashi Japan
- Satoru Kakizaki
- Department of Clinical Research National Hospital Organization Takasaki General Medical Center Takasaki Japan
- Noritomo Shimada
- Division of Gastroenterology and Hepatology Otakanomori Hospital Kashiwa Japan
- Kazuhito Kawata
- Department of Hepatology Hamamatsu University School of Medicine Hamamatsu Japan
- Fujimasa Tada
- Gastroenterology Center Ehime Prefectural Central Hospital Matsuyama Japan
- Hideko Ohama
- Gastroenterology Center Ehime Prefectural Central Hospital Matsuyama Japan
- Kazuhiro Nouso
- Department of Gastroenterology Okayama City Hospital Okayama Japan
- Asahiro Morishita
- Department of Gastroenterology and Hepatology Kagawa University Kagawa Japan
- Akemi Tsutsui
- Department of Hepatology Kagawa Prefectural Central Hospital Takamatsu Japan
- Takuya Nagano
- Department of Hepatology Kagawa Prefectural Central Hospital Takamatsu Japan
- Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo Japan
- Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo Japan
- Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo Japan
- Michitaka Imai
- Department of Gastroenterology Saiseikai Niigata Hospital Niigata Japan
- Hisashi Kosaka
- Department of Surgery Kansai Medical University Osaka Japan
- Atsushi Naganuma
- Department of Gastroenterology National Hospital Organization Takasaki General Medical Center Takasaki Japan
- Yohei Koizumi
- Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine Ehime Japan
- Shinichiro Nakamura
- Department of Internal Medicine Japanese Red Cross Himeji Hospital Himeji Japan
- Masaki Kaibori
- Department of Surgery Kansai Medical University Osaka Japan
- Hiroko Iijima
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Hyogo Medical University Nishinomiya Japan
- Yoichi Hiasa
- Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine Ehime Japan
- DOI
- https://doi.org/10.1002/cam4.5535
- Journal volume & issue
-
Vol. 12,
no. 7
pp. 7772 – 7783
Abstract
Abstract 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 α‐fetoprotein showed that hypertension of any grade (hazard ratio [HR], 0.527; 95% confidence interval [CI], 0.326–0.854; p = 0.009) and α‐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.
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