Liver Cancer (Apr 2024)

Disease etiology impact on outcomes of hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: a real-world, multicenter study

  • Federico Rossari,
  • Toshifumi Tada,
  • Goki Suda,
  • Shigeo Shimose,
  • Masatoshi Kudo,
  • 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 Iavarone,
  • Giuseppe Cabibbo,
  • Margarida Montes,
  • Francesco Giuseppe Foschi,
  • Caterina Vivaldi,
  • Caterina Soldà,
  • Takuya Sho,
  • Takashi Niizeki,
  • Naoshi Nishida,
  • Christoph Steup,
  • 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,
  • Masaaki Kaibori,
  • Hiroko Iijima,
  • Yoichi Hiasa,
  • Mara Persano,
  • Silvia Foti,
  • Silvia Camera,
  • Bernardo Stefanini,
  • Mario Scartozzi,
  • Stefano Cascinu,
  • Andrea Casadei-Gardini,
  • Margherita Rimini

DOI
https://doi.org/10.1159/000537915

Abstract

Read online

Introduction The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post-hoc analyses of IMbrave-150 and metanalyses of clinical trials of PD-1/PD-L1 blockers. As a results, it is not clear whether the first-line systemic treatment atezolizumab plus bevacizumab is equally effective in viral and non-viral patients. Methods We retrospectively analyzed 885 HCC patients treated with first-line A + B from multiple centers from Eastern and Western countries, 53.9% having viral and 46.1% non-viral etiology. Baseline clinical and laboratory characteristics were analyzed with uni- and multi-variate models to explore potential differences on overall survival (OS), time to progression (TTP), disease control rates based on etiology and to identify putative prognostic factors in etiology subgroups. Treatment toxicities and access to second-line treatments and outcomes were also reported and compared between etiologies. Results Overall, no statistically significant differences were found in OS (mOS: viral 15.9 months; non-viral 16.3 months), TTP (mTTP: viral 8.3 months; non-viral 7.2 months), and disease control rates (DCR: viral 78.1%; non-viral 80.8%) based on etiology. Prognostic factors of survival and progression were mainly shared between viral and non-viral etiologies, including alpha-fetoprotein, aspartate transaminase, neutrophil-to-lymphocyte ratio (NLR) and ALBI score. Exploratory analyses highlighted a possible stronger association of immunological factors, i.e. NLR and eosinophil count, to treatment outcomes in viral patients. The toxicity profile, the access to and type of second-line treatments and their outcome in terms of OS almost overlap in the two etiology subgroups. Conclusion Atezolizumab plus bevacizumab efficacy does not vary according to underlying etiology of HCC in a multicenter, real-world population, matching recent post-hoc findings from the IMbrave-150 trial. Preliminary analyses suggest that some prognostic factors differ between viral and non-viral patients, potentially due to biological and immunological differences. Prospective and comparative trials stratifying by etiology are warranted to validate these findings and guide clinical practice.