955P - Association of skeletal muscle mass with safety and efficacy of atezolizumab (atezo) plus bevacizumab (bev) in Japanese patients (pts) with unresectable hepatocellular carcinoma (uHCC): Results from the ELIXIR study

Background

The IMbrave150 study established Atezo+Bev as the standard of care for uHCC pts. However, more clinical practice data is needed. We conducted the ELIXIR study to prospectively evaluate the safety and efficacy of Atezo+Bev in clinical practice in Japan. Here, we report on the association between skeletal muscle mass and the safety and efficacy of Atezo+Bev.

Methods

Among the 510 pts in this multicenter, prospective, observational study, those who agreed to a physical activity assessment were included. We used skeletal muscle mass index (SMI) at the middle of L3 level to assess muscle mass. SMI was measured at baseline and approximately 6 weeks after atezo+bev administration. Pts were divided into two groups based on SMI change: greater than the median (non-decrease group) or less than the median (decrease group). We evaluated the adverse events of special interest (AESI) and other AEs and progression-free survival (PFS) of Atezo+ Bev in the two groups. To reduce immortal time bias, landmark analysis at 6 weeks was performed in the efficacy analysis.

Results

104 pts were enrolled from April 2021 to February 2022, and 97 were analyzed. The median SMI change was -1.3% (range -19.0%, 10.9%). Any-grade AESI were slightly more common in the decrease group (39.6% vs. 51.0%), while the frequency of grade ≥3 AESI was similar in both groups (29.2% vs. 32.7%). No AESI differed in frequency by more than 5% between the two groups. Other any-grade AEs more than 5% higher in the decrease group were hypertension (27.1% vs 34.7%), fatigue (10.4% vs 16.3%), eczema (0% vs 6.1%), and rash (0% vs 6.1%). PFS according to RECIST 1.1 was not significantly different between the non-decrease group (median 9.7 mo [95 % CI 7.6, 13.2]) and the decrease group (median 11.7 mo [95 % CI 7.9, 12.7]), and PFS according to mRECIST showed a similar trend.

Conclusions

This is the first prospective, pre-specified study to evaluate the association between skeletal muscle mass and the safety and efficacy of Atezo+Bev. These analyses suggest that a decrease in SMI at approximately 6 weeks after Atezo+Bev administration does not have a clinically meaningful impact on its safety and efficacy.

Clinical trial identification

UMIN000043463.

Editorial acknowledgement

Legal entity responsible for the study

Chugai Pharmaceutical Co., Ltd.

Funding

Chugai Pharmaceutical Co., Ltd.

Disclosure

A. Hiraoka: Financial Interests, Personal, Invited Speaker, Lecture fee: Chugai, Lilly; Financial Interests, Personal, Invited Speaker, Lecture Fee: AstraZeneca. H. Aikata: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd. 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: Eisai Co., Ltd., 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. 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; 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. N. Morimoto: Financial Interests, Personal, Invited Speaker: Chugai Parma., AbbVie, Eisai; Financial Interests, Personal and Institutional, Research Grant: AbbVie, Eisai. K. Tsuchiya: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Chugai. T. Takehara: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: Chugai. 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. 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, Incyte; Financial Interests, Personal, Advisory Board: Fuji film, Mundi 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. 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 Pharmaceutical, Otsuka Pharmaceutical; 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. T. Yamashita: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Lilly, AstraZeneca; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, MSD, Ono, Abbie, Chugai, Eisai, AstraZeneca. All other authors have declared no conflicts of interest.