Abstract 208P
Background
Intermediate-stage HCC is a heterogeneous disease; therefore, systemic therapy may be preferable for pts with intermediate-stage HCC who are unsuitable for TACE, especially pts with tumors beyond the up-to-seven criteria. REPLACEMENT was a multicenter, phase II study investigating the efficacy and safety of atezo+bev in TACE-naïve pts with intermediate-stage HCC beyond the up-to-seven criteria. This study met its primary endpoint of progression-free survival (PFS) in the primary analysis, but interim overall survival (OS) data were immature. Here, we report the final analysis of OS.
Methods
In this study, eligible pts enrolled between Dec 2020 and Sep 2021 were administered atezo 1200 mg + bev 15 mg/kg q3w until discontinuation due to disease progression, adverse events (AEs), or other reasons. OS follow-up was continued for 2.5 years after enrolment. The primary endpoint was PFS as assessed by investigators using the mRECIST; secondary endpoints were objective response rate (ORR), PFS (RECIST v1.1), OS, and safety.
Results
In total, 74 pts were enrolled (male, 87.8%; mean age, 74.0 years; median [range] maximum tumor diameter by pre-treatment CT, 4.8 [1.0, 13.0] cm; percentage of pts with ≥6 tumors, 31.1%; percentage of pts beyond the up-to-eleven criteria, 33.8%). Median (interquartile range) follow-up was 33.6 (29.7, 36.8) months. Median OS was 33.8 (95%CI: 22.6, not reached) months. 12-month OS rate was 84.7 (95%CI: 74.0, 91.2) %. Median PFS was 9.1 (95%CI: 7.1, 10.2) months (by mRECIST; primary endpoint). ORR (mRECIST) was 40.5 (95%CI: 29.3, 52.6) %; ORR including the effects of conversion therapy was 44.6 (95%CI: 33.0, 56.6) %. The most frequent AEs (of any grade in ≥10% of pts) were hypertension, proteinuria, malaise, anorexia, edema, pruritis, and diarrhea.
Conclusions
The final analysis shows atezo+bev provides promising clinical benefits to pts with TACE-unsuitable intermediate-stage HCC beyond the up-to-seven criteria. Results of the subgroup analysis of OS will be presented.
Clinical trial identification
jRCTs071200051.
Editorial acknowledgement
No
Legal entity responsible for the study
Chugai Pharmaceutical Co., Ltd.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
T. Yamashita: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Lilly, AstraZeneca; Financial Interests, Institutional, Local PI: Bristol-Myers, MSD, Ono, Abbie, Chugai, Eisai, AstraZeneca. K. Ueshima: Financial Interests, Personal, Invited Speaker, Concurrent roles with an advisory board: Chugai, Eisai, Takeda, Lilly Japan; Financial Interests, Personal, Invited Speaker: Astra-Zeneca, Otsuka, Taiho, Sumitomo, MSD, Kowa, EA pharma, AbbVie, Aska, Boston Scientific Japan; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Local PI: Chugai. K. Tsuchiya: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Chugai. N. Kato: Financial Interests, Personal, Invited Speaker: Gilead Sciences Inc., AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Eisai Co., Ltd., Aska Pharmaceutical Co., Ltd., Tsumura & Co., Mochida Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., Covidien Japan Inc., Eli Lilly Japan K.K., Nobelpharma Co., Ltd., Kowa Company, Ltd., Incyte Biosciences Japan GK, Yakult Honsha Co.,Ltd., Olympus Marketing, Inc., Taisho Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Daiichi Sankyo Co., Ltd., Bayer Yakuhin Ltd., EA Pharma Co., Ltd., Asahi Kasei Pharma Co., Ltd.; Financial Interests, Institutional, Research Grant: AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., Eisai Co., Ltd., Tsumura & Co., Nippon Kayaku Co., Ltd., JIMRO Co., Ltd., Kowa Company, Ltd. K. Ohkawa: Financial Interests, Personal, Invited Speaker: Gilead, Eisai, Chugai, AstraZeneca, Incyte; Financial Interests, Personal, Research Grant: Sumitomo Chemical. T. Kuzuya: Financial Interests, Personal, Other, speaker fee: Chugai Pharmaceutical Co. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai, Nihon Servier, Novartis, Bristol Myers Squibb, MSD, Boehringer Ingelheim, Astellas Pharma, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Fujifilm Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan, Nobelpharma, EA Pharma; Financial Interests, Institutional, Coordinating PI: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus. N.V., Merck Biopharma, Boehringer Ingelheim, Invitae, Nobelpharma; Financial Interests, Personal, Steering Committee Member: Chugai, Nihon Servier, Takeda, Novartis, Eisai, Rakuten Medical. H. Aikata: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd. A. Hiraoka: Financial Interests, Personal, Invited Speaker: Chugai, AstraZeneca, Lilly. M. Moriguchi: Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K.; Financial Interests, Institutional, Local PI: MSD K.K. Eisai Co., Ltd., Bristol Myers Squibb K.K., AstraZeneca K.K., Eli Lilly K.K., Eisai Co., Ltd.; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical Company Limited, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd. S. Ogasawara: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Chugai; Financial Interests, Personal, Research Grant: Eisai. K. Yamamoto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, CMIC holdings, Johokiko, AstraZeneca plc, Pfizer; Financial Interests, Personal, Other, Statistical consultation: Craif, Kanagawa Prefectural Hospital Organization; Financial Interests, Institutional, Other, unlimited grant: Taiho Pharmaceutical, Euro Doctor Concierge, LLC; Financial Interests, Institutional, Other, Unlimited grant: Takeda Pharmaceutical, Daiichi Sankyo, Kyowa Kirin, Chugai Phamaceutical, Otsuka Phamaceutical; Financial Interests, Personal, Advisory Board: Delta fly farma, SRL Medisearch lnc., Fujifilm Toyama Chemical Co., Ltd., Takeda Pharmaceutical Company Limited, TME Therapeutics Inc.; Financial Interests, Personal, Writing Engagement: Tokyo Shoseki Co., Ltd. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. All other authors have declared no conflicts of interest.