Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab
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 At...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-04-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5535 |
| _version_ | 1827958737286987776 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Toshifumi Tada |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:41:04Z |
| format | Article |
| id | doaj.art-a7cf1ac5e21f496d9993c6013e712e6a |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T15:41:04Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-a7cf1ac5e21f496d9993c6013e712e6a2023-04-27T10:12:43ZengWileyCancer Medicine2045-76342023-04-011277772778310.1002/cam4.5535Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumabToshifumi Tada0Takashi Kumada1Atsushi Hiraoka2Masashi Hirooka3Kazuya Kariyama4Joji Tani5Masanori Atsukawa6Koichi Takaguchi7Ei Itobayashi8Shinya Fukunishi9Kunihiko Tsuji10Toru Ishikawa11Kazuto Tajiri12Hironori Ochi13Satoshi Yasuda14Hidenori Toyoda15Chikara Ogawa16Takashi Nishimura17Takeshi Hatanaka18Satoru Kakizaki19Noritomo Shimada20Kazuhito Kawata21Fujimasa Tada22Hideko Ohama23Kazuhiro Nouso24Asahiro Morishita25Akemi Tsutsui26Takuya Nagano27Norio Itokawa28Tomomi Okubo29Taeang Arai30Michitaka Imai31Hisashi Kosaka32Atsushi Naganuma33Yohei Koizumi34Shinichiro Nakamura35Masaki Kaibori36Hiroko Iijima37Yoichi Hiasa38Division of Gastroenterology and Hepatology, Department of Internal Medicine Hyogo Medical University Nishinomiya JapanDepartment of Nursing Gifu Kyoritsu University Ogaki JapanGastroenterology Center Ehime Prefectural Central Hospital Matsuyama JapanDepartment of Gastroenterology and Metabology Ehime University Graduate School of Medicine Ehime JapanDepartment of Gastroenterology Okayama City Hospital Okayama JapanDepartment of Gastroenterology and Hepatology Kagawa University Kagawa JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo JapanDepartment of Hepatology Kagawa Prefectural Central Hospital Takamatsu JapanDepartment of Gastroenterology Asahi General Hospital Asahi JapanDepartment of Gastroenterology Osaka Medical and Pharmaceutical University Osaka JapanCenter of Gastroenterology Teine Keijinkai Hospital Sapporo JapanDepartment of Gastroenterology Saiseikai Niigata Hospital Niigata JapanDepartment of Gastroenterology Toyama University Hospital Toyama JapanHepato‐biliary Center Japanese Red Cross Matsuyama Hospital Matsuyama JapanDepartment of Gastroenterology and Hepatology Ogaki Municipal Hospital Ogaki JapanDepartment of Gastroenterology and Hepatology Ogaki Municipal Hospital Ogaki JapanDepartment of Gastroenterology Japanese Red Cross Takamatsu Hospital Takamatsu JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine Hyogo Medical University Nishinomiya JapanDepartment of Gastroenterology Gunma Saiseikai Maebashi Hospital Maebashi JapanDepartment of Clinical Research National Hospital Organization Takasaki General Medical Center Takasaki JapanDivision of Gastroenterology and Hepatology Otakanomori Hospital Kashiwa JapanDepartment of Hepatology Hamamatsu University School of Medicine Hamamatsu JapanGastroenterology Center Ehime Prefectural Central Hospital Matsuyama JapanGastroenterology Center Ehime Prefectural Central Hospital Matsuyama JapanDepartment of Gastroenterology Okayama City Hospital Okayama JapanDepartment of Gastroenterology and Hepatology Kagawa University Kagawa JapanDepartment of Hepatology Kagawa Prefectural Central Hospital Takamatsu JapanDepartment of Hepatology Kagawa Prefectural Central Hospital Takamatsu JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine Nippon Medical School Tokyo JapanDepartment of Gastroenterology Saiseikai Niigata Hospital Niigata JapanDepartment of Surgery Kansai Medical University Osaka JapanDepartment of Gastroenterology National Hospital Organization Takasaki General Medical Center Takasaki JapanDepartment of Gastroenterology and Metabology Ehime University Graduate School of Medicine Ehime JapanDepartment of Internal Medicine Japanese Red Cross Himeji Hospital Himeji JapanDepartment of Surgery Kansai Medical University Osaka JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine Hyogo Medical University Nishinomiya JapanDepartment of Gastroenterology and Metabology Ehime University Graduate School of Medicine Ehime JapanAbstract 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.https://doi.org/10.1002/cam4.5535adverse eventatezolizumab plus bevacizumabhepatocellular carcinomasurvival |
| spellingShingle | 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 Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab Cancer Medicine adverse event atezolizumab plus bevacizumab hepatocellular carcinoma survival |
| title | Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab |
| title_full | Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab |
| title_fullStr | Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab |
| title_full_unstemmed | Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab |
| title_short | Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab |
| title_sort | adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab |
| topic | adverse event atezolizumab plus bevacizumab hepatocellular carcinoma survival |
| url | https://doi.org/10.1002/cam4.5535 |
| work_keys_str_mv | AT toshifumitada adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT takashikumada adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT atsushihiraoka adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT masashihirooka adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT kazuyakariyama adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT jojitani adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT masanoriatsukawa adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT koichitakaguchi adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT eiitobayashi adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT shinyafukunishi adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT kunihikotsuji adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT toruishikawa adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT kazutotajiri adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT hironoriochi adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT satoshiyasuda adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT hidenoritoyoda adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT chikaraogawa adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT takashinishimura adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT takeshihatanaka adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT satorukakizaki adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT noritomoshimada adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT kazuhitokawata adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT fujimasatada adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT hidekoohama adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT kazuhironouso adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT asahiromorishita adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT akemitsutsui adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT takuyanagano adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT norioitokawa adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT tomomiokubo adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT taeangarai adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT michitakaimai adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT hisashikosaka adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT atsushinaganuma adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT yoheikoizumi adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT shinichironakamura adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT masakikaibori adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT hirokoiijima adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab AT yoichihiasa adverseeventsaspotentialpredictivefactorsoftherapeuticactivityinpatientswithunresectablehepatocellularcarcinomatreatedwithatezolizumabplusbevacizumab |