83P - Impact of viral aetiology in the phase III HIMALAYA study of tremelimumab (T) plus durvalumab (D) in unresectable hepatocellular carcinoma (uHCC)

Background

In HIMALAYA (NCT03298451), a single priming dose of T plus D (STRIDE) significantly improved overall survival (OS) vs sorafenib (S), and D was noninferior to S in uHCC (Abou-Alfa et al. NEJM Evid 2022; https://doi.org/10.1056/EVIDoa2100070). Viral aetiology is associated with hepatic impairment in HCC development and may influence immunotherapy activity. Thus, we analysed the impact of viral aetiology on clinical outcomes.

Methods

This exploratory analysis assessed STRIDE, D and S in patients (pts) with HBV (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA), HCV or nonviral/other (NV) aetiology. OS hazard ratios (HRs) were calculated using a Cox proportional hazards model. As subsets were not sized for formal comparisons, no multiplicity adjustments were made. A post hoc multivariate analysis was used to identify chance imbalances in key prognostic factors that may bias estimated treatment effects.

Results

Baseline demographic and disease characteristics were similar across treatment arms in the HBV and NV subsets. However, in the HCV group, multivariate analysis identified imbalances in two prognostic variables: extrahepatic spread (EHS; more frequent for STRIDE than S) and ALBI (score ≥2 more frequent for STRIDE and D than S). OS and progression-free survival were improved with STRIDE vs S in the HBV and NV groups, but not in the HCV group (Table). Using a stratified Cox proportional hazards model to account for imbalances in EHS and ALBI in the HCV subset, OS HRs favoured STRIDE vs S. OS HRs continued to favour STRIDE when adjusting for EHS and ALBI in the other groups. Results for D vs S showed similar trends to those for STRIDE vs S (Table) Table: 83P

^aAdjusted for EHS and ALBI.^bn=160; one pt with missing ALBI score excluded.

Conclusions

In HIMALAYA, OS favoured STRIDE vs S (HR <1) for all aetiologies when subsets were adjusted for prognostic factor imbalances in the HCV cohort; similar trends were observed with D vs S across subsets. These results confirm the benefits of STRIDE and D in pts with uHCC, irrespective of underlying aetiology.

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 Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZenceca.

Disclosure

S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, Astra-Zeneca, MSD; Financial Interests, Personal, Invited Speaker: Astra-Zeneca, MSD, Eisai, Roche, IPSEN, BMS, Bayer; Financial Interests, Personal, Research Grant: Eisai, MSD, IPSEN, Bayer, SIRTEX. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, MSD; Financial Interests, Institutional, Research Grant: Otsuka, Sumitomo Dainippon Pharma, EA Pharma, Taiho, Eisai, AbbVie, Gilead Sciences, Takeda, GE Healthcare, Chugai. B. Sangro: Financial Interests, Personal, Advisory Board: Astra Zeneca, BMS, Boston Scientific, Eisai, Ipsen, Roche, Sirtex, Terumo, Incyte, Bayer; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, BMS, Incyte, Astra Zeneca, Bayer, Astra Zeneca, BMS, Boston Scientific, Roche, Sirtex; Financial Interests, Institutional, Research Grant: BMS, Sirtex; Financial Interests, Institutional, Invited Speaker: Adaptimmune; Non-Financial Interests, Personal, Invited Speaker: International Liver Cancer Association. R.K. Kelley: Financial Interests, Personal, Advisory Board, Compensation for service on advisory board in 2019: Genentech/Roche; Financial Interests, Personal, Other, IDMC membership 2018-2020: Genentech/Roche; Financial Interests, Personal, Advisory Board, 2020: Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory board member in 2021: Kinnate; Financial Interests, Institutional, Invited Speaker: Agios, Agios, Astra Zeneca, Astra Zeneca, Bayer, BMS, Eli Lilly, Exelixis, EMD Serono, Genentech/Roche, Merck, Merck, QED, Taiho, Novartis, Relay Therapeutics, Surface Oncology, LOXO Oncology, Astra Zeneca, Merck; Financial Interests, Institutional, Research Grant: Partner Therapeutics; Non-Financial Interests, Personal, Advisory Role, IDMC chair and member: Genentech/Roche; Non-Financial Interests, Personal, Principal Investigator: Exelixis, Astra Zeneca; Non-Financial Interests, Personal, Advisory Role, IDMC member: Merck. J. Furuse: Financial Interests, Personal, Research Grant: from 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, Consultant Fee: 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. J. Park: Financial Interests, Personal, Member: Roche, AstraZeneca, Bayer; Financial Interests, Personal and Institutional, Other, Clinical Study: BMS, Ono, Roche, AtraZeneca, MSD, Exelisix; Financial Interests, Personal and Institutional, Other, Investigator-initiated trial: BMS; Financial Interests, Personal, Other, Symposium Chair: Bayer, Ipsen, Roche; Financial Interests, Personal, Other, Co-author: Guebert. P. Sunpaweravong: Financial Interests, Personal, Advisory Board: Roche, Eisai, BMS, AstraZeneca, MSD, Ipsen, Pfizer; Financial Interests, Personal, Invited Speaker: Novartis, BMS, Mundipharma, Bayer. T. Yau: Financial Interests, Personal, Advisory Board, Honorarium: BMS, MSD, AstraZeneCa, Roche. T. Kawaoka: Financial Interests, Institutional, Funding: AstraZeneca. A. Cheng: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Bayer Healthcare, AstraZeneca, Genentech/Roche, Merck Sharp Dohme, BeiGene, Ltd., EXELIXIS Ltd., IPSEN Innovation, F. Hoffmanna-La ROCHE Ltd.; Financial Interests, Personal, Invited Speaker: Eisai, Ono Pharmaceutical, Bayer Yakuhin Ltd., Novartis, Amgen Taiwan, Chugai Pharmaceutical; Financial Interests, Personal, Other, Travel: IQVIA. S. Azevedo: Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Bristol Myers Squibb, MSD, Novartis, Pfizer, and Roche/Genentech. M.E. Reig Monzon: Financial Interests, Personal and Institutional, Advisory Role: Bayer, BMS, Roche, Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Bayer, BMS, Roche, Lilly; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Ispen; Financial Interests, Personal, Advisory Role: Ispen, AstraZeneca, Universal DX; Financial Interests, Personal, Invited Speaker: Gilead, Eisai, BTG. E. Assenat: Financial Interests, Personal, Advisory Board: AstraZeneca, Ipsen, Bayer, Roche. M. Yarchoan: Financial Interests, Personal and Institutional, Advisory Role: Genentech, Exelixis; Financial Interests, Personal and Institutional, Research Grant: Genentech, Exelixis; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Incyte; Financial Interests, Personal, Advisory Role: Eisai, AstraZeneca, Replimune, Hepion. A.R. He: Financial Interests, Personal, Research Grant: Genentech and Merck; Financial Interests, Personal, Other, Consultant Fee: AstraZeneca, Bristol Myers Squibb, and Genentech/Roche, and Speakers’ bureau from Bristol Myers Squibb and Eisai. M. Makowsky: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. D. Ran: Financial Interests, Personal, Full or part-time Employment: 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.