79P - Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase III HIMALAYA study

Background

In the Phase 3 HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), a single priming dose of tremelimumab (anti-CTLA-4) plus durvalumab (anti-PD-L1) in the STRIDE regimen significantly improved overall survival vs sorafenib, and durvalumab monotherapy was noninferior to sorafenib (Abou-Alfa et al. NEJM Evid 2022; https://doi.org/10.1056/EVIDoa2100070). Liver function is frequently impaired in patients with HCC, and it is important to evaluate the efficacy and safety of systemic therapies for these patients.

Methods

HIMALAYA included patients with Child-Pugh Score class A. This subgroup analysis of HIMALAYA assessed outcomes in patients classified by baseline albumin-bilirubin (ALBI) scores (log10[bilirubin]) x 0.66 - albumin x 0.085), an objective measure based on laboratory values: Grade 1 (score ≤-2.60), Grade 2 (score >-2.60 to ≤-1.39) and Grade 3 (score >-1.39). Due to small sample size, outcomes for the ALBI Grade 3 subgroup (STRIDE, n=1; durvalumab, n=2; sorafenib, n=1) were combined with the ALBI Grade 2 subgroup.

Results

Baseline demographics and disease characteristics were similar across treatment arms. Efficacy outcomes across subgroups are summarised (Table). Safety was consistent with the full analysis set. Table: 79P

Efficacy outcomes across ALBI subgroups

*Vs sorafenib; calculated using Cox proportional hazards model adjusted for treatment, aetiology, ECOG performance status and macrovascular invasion. DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; IQR, interquartile range; m, median; NR, not reached; ORR, objective response rate; OS, overall survival; TTR, time to response.

Conclusions

STRIDE showed a favourable benefit-risk profile compared with sorafenib across ALBI subgroups. STRIDE and durvalumab may represent new treatment options in uHCC for patients with less optimal liver function.

Clinical trial identification

NCT03298451.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Claire Tinderholm, PhD, of CMC Connect, McCann Health Medical Communications, with funding from AstraZeneca, in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

A. Vogel: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Eisai, Ipsen, ncyte, PierreFabre, Lilly, Imaging Equipment Ltd. (AAA), Roche, MSD, Beigene, Jiangsu Hengrui Medicines.; Financial Interests, Personal, Advisory Board: Roche, Bayer, BMS, MSD, Eisai, Ipsen, Incyte, Pierre Fabre, Lilly, AstraZeneca, Boston Scientific, Sirtex, Daichi-Sankyo. S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD; Financial Interests, Personal, Invited Speaker: Astra-Zeneca, MSD, Eisai, Roche, Ipsen, BMS, Bayer; Financial Interests, Personal, Research Grant: Eisai, MSD, Ipsen, Bayer, SIRTEX. J. Furuse: Financial Interests, Personal, Other, Grant and research support: Astellas, Chugai Pharma, Daiichi Sankyo, Eisai, Incyte Japan, J-Pharma, Merck Bio, Mochida, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Sanofi, Sumitomo Dainippon Bayer, and Yakult Honsha; Financial Interests, Personal, Other, Consulting fees: Bayer, Chugai Pharma, Daiichi Sankyo, EA Pharma, Eisai, Eli Lilly Japan, Incyte Japan, Kyowa Hakko Kirin, MSD, Mylan EPD, Novartis Pharma, Ono Pharmaceutical, Pfizer, Sanofi, Servier Japan, Taiho Pharmaceutical, Takeda, Teijin Pharma, and Yakult Honsha. M. Varela: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Bayer, Eisai-MSD, Bristol Myers Squibb, and Roche; Financial Interests, Personal, Other, Honoraria: AbbVie, Bayer, Boston, Eisai-MSD, and Gilead; Financial Interests, Personal, Other, Travel expenses: AstraZeneca and Bayer. J.H. Kim: Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Sanofi-Aventis, Roche diagnostics; Financial Interests, Personal, Advisory Board, speaker at advisory board meeting: Everest Medicine; Financial Interests, Personal, Advisory Board: Yuhan, Pfizer, Roche Korea, Novartis, Eisai Co., Ltd., Daiichi Sankyo Korea; Financial Interests, Institutional, Research Grant, Research grant for investigator-sponsored clinical trial (I am the coordinating PI): Ono Pharma Korea Co. Ltd.; Non-Financial Interests, Personal, Principal Investigator, Coordinating PI of Investigator sponsored clinical study - drug supplies from Roche: Roche. S. Tanasanvimon: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, MSD, Novartis, and Roche. M.E. Reig Monzon: Financial Interests, Personal, Other, Consulting fees: Bayer - Shering Pharma, Ipsen, BMS, Roche, AstraZeneca, Lilly, BTG; Financial Interests, Personal, Other, Paid conferences: Bayer-Shering Pharma, BMS, Roche, Lilly, Gillead, Eisai; Financial Interests, Personal, Research Grant: Bayer-Shering Pharma, Ipsen. F. Dayyani: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Natera, Exelixis, Genentech; Financial Interests, Personal, Speaker’s Bureau: Deciphera, Eisai, Exelixis, Ipsen, Servier, Natera, Sirtex; Financial Interests, Personal, Other, Contracted research: AstraZeneca, BMS, Taiho, Exelixis, Merck, Trishula, Natera, Ipsen. M. Makowsky: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Marcovitz: Financial Interests, Personal, Full or part-time Employment, Former employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Negro: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G.K. Abou-Alfa: Financial Interests, Personal, Advisory Board: Adicet, Alnylam, Astra Zeneca, Autem, Beigene, Berry Genomics, Boehringer Ingelheim, Celgene, Cend, CytomX, Eisai, Eli Lilly, Exelixis, Flatiron, Genentech/Roche, Genoscience, Helio, Helsinn, Incyte, Ipsen, Merck, Nerviano, Newbridge, Novartis, QED, Redhill, Rafael, Servier, Silenseed, Sobi, Vector, Yiviva; Financial Interests, Personal, Other, IP License: PCT/US2014/031545 filed on March 24, 2014, and priority application Serial No.: 61/804,907; Filed: March 25, 2013; Financial Interests, Institutional, Research Grant: Arcus, Astra Zeneca, BioNtech, BMS, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, Yiviva; Non-Financial Interests, Personal, Principal Investigator: Astra Zeneca, Yiviva, QED. All other authors have declared no conflicts of interest.