TY - JOUR
T1 - Protocol of the IMPACT study
T2 - randomized, multicenter, phase 3 study evaluating the efficacy of immunotherapy (Atezolizumab) plus anti-VEGF therapy (Bevacizumab) in combination with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma
AU - Kodama, Yoshihisa
AU - Ueshima, Kazuomi
AU - Moriguchi, Michihisa
AU - Inaba, Yoshitaka
AU - Yamashita, Tatsuya
AU - Iwamoto, Hideki
AU - Ueno, Makoto
AU - Ogasawara, Sadahisa
AU - Kuzuya, Teiji
AU - Kodama, Takahiro
AU - Sato, Yozo
AU - Tada, Toshifumi
AU - Tsuchiya, Kaoru
AU - Nishiofuku, Hideyuki
AU - Yamakado, Koichiro
AU - Sone, Miyuki
AU - Ikeda, Masafumi
AU - Takehara, Tetsuo
AU - Hamano, Tetsutaro
AU - Kudo, Masatoshi
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Background: Atezolizumab plus bevacizumab is recommended as a first-line treatment for unresectable hepatocellular carcinoma (uHCC). A subgroup analysis of the IMbrave150 trial showed shorter overall survival (OS) in uHCC patients with stable disease (SD) than patients with complete response (CR) or partial response (PR) after atezolizumab plus bevacizumab. Improving OS in patients with SD is an unmet medical need. Transcatheter arterial chemoembolization (TACE) may enhance treatment efficacy by controlling intrahepatic lesions and activating anti-tumor immunity. The IMPACT study aims to evaluate whether combining atezolizumab plus bevacizumab with TACE improves OS in patients with SD. Methods: IMPACT is a multicenter, phase 3 study being conducted in Japan, recruiting uHCC patients aged ≥ 18 years with Barcelona Clinic Liver Cancer stage A (single tumor ≥ 5 cm only, TACE unsuitable), stage B (TACE unsuitable) or stage C (excluding Vp3 or 4), Child–Pugh A liver function, and no prior systemic therapy. After 12 weeks of atezolizumab plus bevacizumab treatment as induction therapy, patients are being divided into two cohorts based on response: a randomized cohort for patients who achieve SD, or an atezolizumab plus bevacizumab followed by curative conversion (ABC-conversion) cohort for patients who achieve CR or PR. Patients in the randomized cohort are receiving atezolizumab plus bevacizumab and intrahepatic control TACE (Group A), or continuing atezolizumab plus bevacizumab (Group B). Patients in the ABC-conversion cohort are receiving atezolizumab plus bevacizumab. All cohorts can be considered for curative conversion therapies for residual tumors if these therapies are considered curative, in the patient's best interests, and deemed necessary by the investigator. The primary endpoint is OS for the randomized cohort and conversion rate for the ABC-conversion cohort. Secondary endpoints in both cohorts include progression-free survival, objective response rate, duration of response, time to CR, and safety. The study is expected to last 6.5 years from June 2023. Discussion: IMPACT is evaluating the efficacy of combination therapy with atezolizumab plus bevacizumab and TACE, as well as exploring the efficacy of curative conversion therapy. The results should contribute to establishing a response-guided treatment strategy for uHCC by determining optimal treatment according to the therapeutic effect of atezolizumab plus bevacizumab. Trial registration: Japan Registry of Clinical Trials (jRCT), identifier: jRCTs051230037. Registered 13 June 2023. Protocol version: 8 May 2024; version 1.4.
AB - Background: Atezolizumab plus bevacizumab is recommended as a first-line treatment for unresectable hepatocellular carcinoma (uHCC). A subgroup analysis of the IMbrave150 trial showed shorter overall survival (OS) in uHCC patients with stable disease (SD) than patients with complete response (CR) or partial response (PR) after atezolizumab plus bevacizumab. Improving OS in patients with SD is an unmet medical need. Transcatheter arterial chemoembolization (TACE) may enhance treatment efficacy by controlling intrahepatic lesions and activating anti-tumor immunity. The IMPACT study aims to evaluate whether combining atezolizumab plus bevacizumab with TACE improves OS in patients with SD. Methods: IMPACT is a multicenter, phase 3 study being conducted in Japan, recruiting uHCC patients aged ≥ 18 years with Barcelona Clinic Liver Cancer stage A (single tumor ≥ 5 cm only, TACE unsuitable), stage B (TACE unsuitable) or stage C (excluding Vp3 or 4), Child–Pugh A liver function, and no prior systemic therapy. After 12 weeks of atezolizumab plus bevacizumab treatment as induction therapy, patients are being divided into two cohorts based on response: a randomized cohort for patients who achieve SD, or an atezolizumab plus bevacizumab followed by curative conversion (ABC-conversion) cohort for patients who achieve CR or PR. Patients in the randomized cohort are receiving atezolizumab plus bevacizumab and intrahepatic control TACE (Group A), or continuing atezolizumab plus bevacizumab (Group B). Patients in the ABC-conversion cohort are receiving atezolizumab plus bevacizumab. All cohorts can be considered for curative conversion therapies for residual tumors if these therapies are considered curative, in the patient's best interests, and deemed necessary by the investigator. The primary endpoint is OS for the randomized cohort and conversion rate for the ABC-conversion cohort. Secondary endpoints in both cohorts include progression-free survival, objective response rate, duration of response, time to CR, and safety. The study is expected to last 6.5 years from June 2023. Discussion: IMPACT is evaluating the efficacy of combination therapy with atezolizumab plus bevacizumab and TACE, as well as exploring the efficacy of curative conversion therapy. The results should contribute to establishing a response-guided treatment strategy for uHCC by determining optimal treatment according to the therapeutic effect of atezolizumab plus bevacizumab. Trial registration: Japan Registry of Clinical Trials (jRCT), identifier: jRCTs051230037. Registered 13 June 2023. Protocol version: 8 May 2024; version 1.4.
KW - Atezolizumab
KW - Bevacizumab
KW - Conversion
KW - Hepatocellular carcinoma
KW - Multidisciplinary treatment
KW - Protocol
KW - Study design
KW - Transcatheter arterial chemoembolization
KW - Unresectable
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U2 - 10.1186/s12885-025-13648-5
DO - 10.1186/s12885-025-13648-5
M3 - Article
C2 - 40069616
AN - SCOPUS:105000053262
SN - 1471-2407
VL - 25
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 434
ER -
