153P - IMbrave150: Exploratory analyses for investigating associations between overall survival (OS) and depth of response (DpR) or duration of response (DoR) in patients (pts) with unresectable hepatocellular carcinoma (HCC)

Background

The IMbrave150 study (Finn RS, NEJM 2020; Cheng AL, J Hepatol 2022) established atezolizumab (atezo) plus bevacizumab (bev) as the global standard of care in pts with unresectable HCC. Previously, tumour response by RECIST 1.1 was reported to be associated with OS in pts treated with atezo+bev (Ducreux M, ASCO 2021; Lim M, Hepatology 2023). Here, we report exploratory analyses investigating associations between OS and DpR or DoR.

Methods

DpR was defined as the maximum tumour shrinkage from baseline based on the sum of longest diameters as assessed by an independent review facility (IRF) per RECIST 1.1. DoR was defined as time from first documented complete or partial response by IRF assessment per RECIST 1.1 until disease progression or death, whichever occurred first. Associations between OS and DpR or DoR were evaluated by scatterplot. The Kaplan-Meier method and proportional hazard modelling were also used to estimate the survival distribution and hazard ratio (HR). The DpR analysis included pts who survived ≥6 mo to reduce immortal time bias.

Results

Of the 336 and 165 pts randomised to the atezo+bev and sorafenib arms, respectively, 264 and 99 pts who survived ≥6 mo were included in the DpR analysis, and 97 and 18 pts were included in the DoR analysis. The scatterplot of DpR-OS indicated that the association between DpR and OS was not conclusive. However, the 6-mo landmark analysis for the atezo+bev arm showed that the tumour shrinkage population (DpR <0%) had a better OS than the non-tumour shrinkage population (DpR ≥0%; HR, 0.29; 95% CI: 0.19, 0.44). A similar trend was observed for the 12-mo landmark analysis (HR, 0.31; 95% CI: 0.17, 0.55). For DoR, the scatterplot of DoR-OS showed that DoR was generally associated with OS, as expected by the definition of the endpoints. However, some pts had longer OS despite shorter DoR, and interpretation was limited due to censored pts.

Conclusions

Although these exploratory analyses have several limitations, including immortal time bias, DpR and DoR tend to be associated with OS, and tumour shrinkage may be an additional outcome measure of treatment efficacy.

Clinical trial identification

NCT03434379.

Editorial acknowledgement

Editorial assistance for this abstract was provided by Megan Zborowski of Health Interactions and funded by Chugai Pharmaceutical Co., Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd. and Chugai Pharmaceutical Co., Ltd.

Funding

F. Hoffmann-La Roche Ltd. and Chugai Pharmaceutical Co., Ltd.

Disclosure

M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, EA Pharma, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. T. Yamashita: Financial Interests, Personal, Speaker’s Bureau: Bayer, Chugai Pharmaceutical Co. Ltd. ; Financial Interests, Personal, Research Funding: F Hoffmann-La Roche Ltd. R.S. Finn: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, BMS, CSTONE, Eisai, Exelixis, Eli Lilly, Merck, Pfizer, Roche, Genentech, Hengrui; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, Bayer; Financial Interests, Institutional, Research Grant: Bayer, Eisai, Eli Lilly, BMS; Financial Interests, Institutional, Coordinating PI: Roche, Pfizer, Merck. P.R. Galle: Financial Interests, Personal, Sponsor/Funding: Adaptimmune, AstraZeneca, Bayer, Boston Scientific, BMS, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd, Guerbet, Ipsen, Merck, Sharp & Dohme, Sirtex Medical; Financial Interests, Personal, Other, Honoraria: Adaptimmune, AstraZeneca, Bayer, Boston Scientific, BMS, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Guerbet, Ipsen, Merck Sharp & Dohme, Sirtex Medical; Financial Interests, Personal, Advisory Role: Adaptimmune, AstraZeneca, Bayer, Boston Scientific, BMS, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd, Guerbet, Ipsen, Merck Sharp & Dohme, Sirtex Medical; Financial Interests, Institutional, Research Funding: F Hoffmann-La Roche Ltd, Bayer. M.P. Ducreux: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd, Ipsen, Merck Serono, Pierre Fabre, Servier; Financial Interests, Personal, Other, travel: Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd, Ipsen, Merck Sharp & Dohme, Servier; Financial Interests, Personal, Speaker’s Bureau: Amgen, Bayer, Eli Lilly, F Hoffmann-La Roche Ltd, Ipsen; Financial Interests, Personal, Speaker’s Bureau, F Hoffmann-La Roche Ltd: Merck Serono; Financial Interests, Institutional, Research Funding: F Hoffmann-La Roche Ltd, Bayer. A. Cheng: Financial Interests, Institutional, Research Funding: F Hoffmann-La Roche Ltd. K. Tsuchiya: Financial Interests, Personal, Advisory Role: Chugai Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co. Ltd, Eisai, Eli Lilly, Takeda; Financial Interests, Personal, Research Funding: F Hoffmann-La Roche Ltd. N. Sakamoto: Financial Interests, Personal, Financially compensated role, honoraria: AbbVie, Eisai, Gilead Sciences, Otsuka; Financial Interests, Institutional, Research Funding: Astellas Pharmaceutical, Bayer, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Gilead Sciences, Otsuka, Takeda. S. Hige: Financial Interests, Personal, Speaker, Consultant, Advisor: gilead sciences, AbbVie, Chugai Pharmaceutical Co., LTD. R. Take: Financial Interests, Personal, Full or part-time Employment: Chugai Pharmaceutical Co. Ltd.. K. Yamada: Financial Interests, Personal, Full or part-time Employment: Chugai Pharmaceutical Co. Ltd.. T. Asakawa: Financial Interests, Personal, Full or part-time Employment: Chugai Pharmaceutical Co. Ltd.. Y. Nakagawa: Financial Interests, Personal, Full or part-time Employment: Chugai Pharmaceutical Co. Ltd. M. Ikeda: Financial Interests, Personal, Financially compensated role: Bayer, Chugai Pharmaceutical Co. Ltd, Eisai, Eli Lilly, Takeda; Financial Interests, Personal, Speaker, Consultant, Advisor: Chugai Pharmaceutical Co. Ltd, Eisai; Financial Interests, Personal, Advisory Board: Eli Lilly, Merck Sharp & Dohme, Takeda; Financial Interests, Personal, Research Funding: Bayer, BMS, Chugai Pharmaceutical Co. Ltd, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme, Takeda.