Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice.

Yuka Hayakawa,Nobuharu Tamaki,Jun Itakura,Chiaki Maeyashiki,Koji Yamashita,Namiki Izumi,Tatsuya Kakegawa,Hiroaki Matsumoto,Kento Inada,Sakura Kirino,Yuka Takahashi,Ryuichi Okamoto,Yuki Tanaka,Yasuhiro Asahina,Shun Kaneko,Shun Ishido,Shohei Tanaka,Hiroyuki Nakanishi,Tsubasa Nobusawa,Kenta Takaura,Masayuki Kurosaki,Yutaka Yasui,Kaoru Tsuchiya,Masakazu Higuchi

doi:10.1007/s10637-021-01185-4

Abstract

We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6weeks had a significantly longer TTP assessed by RECIST than those without an AFP response (P = 0.02). Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6weeks could be a predictor of disease progression.

Highlights

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common cause of cancer-related deaths worldwide [1]
The AFP response at 6 weeks could be a predictor of disease progression
Among the 16 patients who received atezolizumab plus bevacizumab as 2nd-line treatment, 15 were treated with lenvatinib as 1st-line treatment and 1 patient who had been treated with cytotoxic agents as systemic chemotherapy received ramucirumab as the 1st-line molecular targeted agent

Summary

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common cause of cancer-related deaths worldwide [1]. VEGF is associated with cancer immune evasion Based on this rationale, the combination of programmed cell death-ligand 1 (PD-L1) (atezolizumab) and VEGF (bevacizumab) pathway inhibition is believed to be the most effective molecular targeted therapy for advanced HCC. In September 2020, atezolizumab plus bevacizumab [9] was approved for patients with u-HCC in Japan and became the recommended 1st-line therapy. We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab as 1st-line and later-line therapies in real-world practice. We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alphafetoprotein (AFP) response in real-world practice

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