Abstract 200P
Background
The interim analysis of the ELIXIR study (median follow-up of 13.6 months) showed the adverse events of special interest (AESIs) and efficacy to be consistent with those reported in the IMbrave150 trial. Here, we report the prespecified final analysis of safety and efficacy outcomes with an additional one year of follow-up.
Methods
This study enrolled patients with uHCC who had been selected to receive Atezo+Bev, were aged 20 years or older, were of Child-Pugh class A, and had received no prior systemic therapy. The primary endpoint was the frequency of AESIs. Secondary endpoints were immune-related adverse events (irAEs), progression-free survival (PFS), objective response rate (ORR), and overall survival (OS).
Results
Between April 2021 and February 2022, 509 patients were enrolled, and 493 patients were analyzed (median age, 73.0 years; Child-Pugh class A5, 67.5%; Barcelona Clinic Liver Cancer stage B, 41.2%, comorbid hypertension, 71.2%; comorbid diabetes, 43.8%). At the final analysis (17 Feb 2024), the median follow-up was 25.7 months (95% CI 24.9, 26.5). AESIs of any grade were observed in 241 patients (48.9% [95%CI: 44.4, 53.4]) and grade ≥3 AESIs were observed in 184 patients (37.3% [95%CI: 33.0, 41.8]). AESIs with a frequency of ≥5% were grade ≥3 hypertension (23.7%), grade ≥3 proteinuria (8.5%), and hypothyroidism (7.1%). irAEs of any grade requiring corticosteroids were observed in 10.3% of patients. The median OS was 26.1 months (95% CI: 21.3, 28.1), and the 12-month survival rate was 78.1%. Median PFS by RECIST v1.1 was 7.6 months (95% CI: 6.3, 8.7), and the ORR by RECIST v1.1 was 28.8% (95% CI: 24.8, 33.0).
Conclusions
The final analysis of the ELIXIR study showed no new safety concerns and efficacy results were comparable to IMbrave150, even in the real-world clinical setting with Japanese patients, many of whom were elderly. These results further support Atezo+Bev as the standard of care for systemic-treatment-naive uHCC patients in Japan.
Clinical trial identification
UMIN000043463.
Editorial acknowledgement
Legal entity responsible for the study
Chugai Pharmaceutical Co., Ltd.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
T. Takehara: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: 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. H. Aikata: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd. T. Kuzuya: Financial Interests, Personal, Other, speaker fee: Chugai Pharmaceutical Co. 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. N. Morimoto: Financial Interests, Personal, Invited Speaker: Chugai Parma., AbbVie, Eisai; Financial Interests, Personal and Institutional, Research Grant: AbbVie, Eisai. Y. Kawamura: Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., Terumo Corporation., AstraZeneca Plc; Non-Financial Interests, Personal, Principal Investigator: Chugai Pharmaceutical Co., Eisai Co., Ltd. K. Tsuchiya: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Chugai. 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. A. Hiraoka: Financial Interests, Personal, Invited Speaker: Chugai, AstraZeneca, Lilly. N. Kokudo: Financial Interests, Personal, Other, Steering committee member for a clinical trial: AstraZeneca. J. Furuse: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bayer, Eisai, Eli Lilly Japan, MSD, Yakult Honsha, Chugai Pharma, Novartis Pharma, AstraZeneca, Pfizer, Takeda, Taiho Pharmaceutical, Sanofi, Mylan EPD, EA Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Teijin pharma, Servier Japan, Incy; Financial Interests, Personal, Advisory Board: Fuji film, Mudi Pharma, Onco Therapy Science, Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Chugai Pharma, Astellas, AstraZeneca, Takara bio, Delta-Fly-Pharma, Incyte Japan; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical, MSD, Merck Bio, J-Pharma, Taiho Pharmaceutical, Takeda, Chugai Pharma, AstraZeneca, Yakult Honsha, Eisai, Daiichi Sankyo, Mochida, Sanofi, Sumitomo Dainippon Bayer, Astellas, Incyte Japan; Financial Interests, Personal, Steering Committee Member: Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Astellas, AstraZeneca, Incyte Japan. 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. T. Yamashita: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Lilly, AstraZeneca; Financial Interests, Institutional, Local PI: Bristol-Myers, MSD, Ono, Abbie, Chugai, Eisai, AstraZeneca. 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. 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.