Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?

Margherita Rimini¹, Mara Persano², Toshifumi Tada³, Goki Suda⁴, Shigeo Shimose⁵, Masatoshi Kudo⁶, Jaekyung Cheon⁷, Fabian Finkelmeier⁸, Ho Yeong Lim⁹, José Presa¹⁰, Gianluca Masi^{11

12}, Changhoon Yoo¹³, Sara Lonardi¹⁴, Fabio Piscaglia¹⁵, Takashi Kumada¹⁶, Naoya Sakamoto⁴, Hideki Iwamoto⁵, Tomoko Aoki⁶, Hong Jae Chon⁷, Vera Himmelsbach⁸, Tiziana Pressiani¹⁷, Margarida Montes¹⁰, Caterina Vivaldi^{11

12}, Caterina Soldà¹⁴, Atsushi Hiraoka¹⁸, Takuya Sho⁴, Takashi Niizeki⁵, Naoshi Nishida⁶, Christoph Steup⁸, Masashi Hirooka¹⁹, Kazuya Kariyama²⁰, Joji Tani²¹, Masanori Atsukawa²², Koichi Takaguchi²³, Ei Itobayashi²⁴, Shinya Fukunishi²⁵, Kunihiko Tsuji²⁶, Toru Ishikawa²⁷, Kazuto Tajiri²⁸, Hironori Ochi²⁹, Satoshi Yasuda³⁰, Hidenori Toyoda³⁰, Chikara Ogawa³¹, Takashi Nishimura³², Takeshi Hatanaka³³, Satoru Kakizaki³⁴, Noritomo Shimada³⁵, Kazuhito Kawata³⁶, Fujimasa Tada¹⁸, Hideko Ohama¹⁸, Kazuhiro Nouso²⁰, Asahiro Morishita²¹, Akemi Tsutsui²³, Takuya Nagano²³, Norio Itokawa²², Tomomi Okubo²², Taeang Arai²², Michitaka Imai²⁷, Hisashi Kosaka³⁷, Atsushi Naganuma³⁸, Yohei Koizumi²⁰, Shinichiro Nakamura³, Masaki Kaibori³⁷, Hiroko Iijima³², Yoichi Hiasa¹⁹, Valentina Burgio³⁹, Lorenza Rimassa^{17

40}, Mario Scartozzi², Stefano Cascinu³⁹, Andrea Casadei-Gardini³⁹

Affiliations

¹ Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, , Vita-Salute San Raffaele University, Milan, Italy. margherita.rimini@gmail.com.
² Medical Oncology, University and University Hospital of Cagliari, Cagliari, Italy.
³ Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
⁴ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
⁵ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan.
⁶ Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan.
⁷ Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.
⁸ Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
⁹ Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea.
¹⁰ Liver Unit-CHTMAD, Vila Real, Portugal.
¹¹ Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy.
¹² Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
¹³ Department of Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
¹⁴ Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
¹⁵ Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
¹⁶ Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
¹⁷ Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
¹⁸ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
¹⁹ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
²⁰ Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
²¹ Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.
²² Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
²³ Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
²⁴ Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
²⁵ Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan.
²⁶ Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
²⁷ Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
²⁸ Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
²⁹ Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.
³⁰ Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
³¹ Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.
³² Division of Gastroenterology and Hepatology, Department of Internal Medicine, , Hyogo Medical University, Nishinomiya, Japan.
³³ Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
³⁴ Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
³⁵ Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.
³⁶ Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
³⁷ Department of Surgery, Kansai Medical University, Osaka, Japan.
³⁸ Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
³⁹ Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, , Vita-Salute San Raffaele University, Milan, Italy.
⁴⁰ Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Emanuele, 20072, Pieve Milan, Italy.

PMID: 36920648
DOI: 10.1007/s11523-023-00953-x

Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?

Margherita Rimini et al. Target Oncol. 2023 Mar.

. 2023 Mar;18(2):221-233.

doi: 10.1007/s11523-023-00953-x. Epub 2023 Mar 15.

Authors

Affiliations

¹ Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, , Vita-Salute San Raffaele University, Milan, Italy. margherita.rimini@gmail.com.
² Medical Oncology, University and University Hospital of Cagliari, Cagliari, Italy.
³ Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
⁴ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
⁵ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan.
⁶ Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan.
⁷ Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.
⁸ Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
⁹ Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea.
¹⁰ Liver Unit-CHTMAD, Vila Real, Portugal.
¹¹ Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy.
¹² Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
¹³ Department of Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
¹⁴ Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
¹⁵ Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
¹⁶ Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
¹⁷ Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
¹⁸ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
¹⁹ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
²⁰ Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
²¹ Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.
²² Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
²³ Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
²⁴ Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
²⁵ Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan.
²⁶ Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
²⁷ Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
²⁸ Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
²⁹ Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.
³⁰ Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
³¹ Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.
³² Division of Gastroenterology and Hepatology, Department of Internal Medicine, , Hyogo Medical University, Nishinomiya, Japan.
³³ Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
³⁴ Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
³⁵ Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.
³⁶ Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
³⁷ Department of Surgery, Kansai Medical University, Osaka, Japan.
³⁸ Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
³⁹ Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, , Vita-Salute San Raffaele University, Milan, Italy.
⁴⁰ Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Emanuele, 20072, Pieve Milan, Italy.

PMID: 36920648
DOI: 10.1007/s11523-023-00953-x

Abstract

Background: Atezolizumab plus bevacizumab has recently been approved as a new first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC).

Objective: We performed a real-world study to evaluate the impact of the IMbrave150 trial inclusion criteria on the safety and efficacy of treatment outside of clinical trials.

Methods: We analyzed patients treated with atezolizumab plus bevacizumab for unresectable HCC from four different countries. No specific inclusion and exclusion criteria were applied, except for the absence of previous systemic therapies for HCC. The entire population was split into two groups according to concordance with the inclusion criteria as reported in the IMbrave150 trial in 'IMbrave150-in' and 'IMbrave150-out' patients, and safety and efficacy in the two groups of patients were evaluated.

Results: Overall, 766 patients were included in the analysis: 561/766 (73%) in the 'IMbrave150-in' group and 205/766 (27%) in the 'IMbrave150-out' group. Median overall survival (OS) and median progression-free survival (PFS) were 16.3 versus 14.3 months (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.35-0.65; p < 0.0001] and 8.3 versus 6.0 months (HR 0.79, 95% CI 0.63-0.99; p = 0.0431) in 'IMbrave150-in' and 'IMbrave150-out' patients, respectively. Multivariate analysis confirmed that patients included in the 'IMbrave150-in' group had significantly longer OS compared with patients included in the 'IMbrave150-out' group (HR 0.76, 95% CI 0.47-0.97; p = 0.0195). In 'IMbrave150-in' patients, the albumin-bilirubin (ALBI) grade was not associated with OS, whereas in 'IMbrave150-out' patients, those with ALBI grade 1 reported a significant benefit in terms of OS compared with those with ALBI grade 2 (16.7 vs. 5.9 months; HR 4.40, 95% CI 2.40-8.08; p > 0.0001). No statistically significant differences were reported in the 'IMbrave150-in' and 'IMbrave150-out' groups in terms of safety profile.

Conclusion: Adherence to the IMbrave150 trial inclusion criteria favorably impacts the prognosis of patients receiving atezolizumab plus bevacizumab. Among patients who did not meet the IMbrave150 inclusion criteria, those with ALBI grade 1 could benefit from the treatment.

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References

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Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?

Affiliations

Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?

Authors

Affiliations

Abstract

References

REFERENCES

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Full Text Sources

Medical