Abstract 714P
Background
In HIMALAYA (NCT03298451), a single, high 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. J Clin Oncol 2022;40(suppl 4). Abs 379). 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: 714P
| OSHR vs S; 95% CI | OSCox-stratifieda HR vs S; 95% CI | Objective response, % | Disease control rate, % | Median time to response, months | Median duration of response, months | ||
| HBV | STRIDE n=122 | 0.64; 0.48–0.86 | 0.64; 0.47–0.86 | 21.3 | 59.0 | 1.9 | 25.7 |
| D n=119 | 0.78; 0.58–1.04 | 0.78; 0.58–1.04 | 14.3 | 49.6 | 1.9 | 9.5 | |
| S n=119 | 5.0 | 48.7 | 2.8 | 17.0 | |||
| HCV | STRIDE n=110 | 1.06; 0.76–1.49 | 0.89; 0.63–1.25 | 35.5 | 65.5 | 3.6 | 13.5 |
| D n=107 | 1.05; 0.75–1.48 | 0.93; 0.66–1.31 | 22.4 | 57.9 | 2.0 | 12.9 | |
| S n=104 | 9.6 | 70.2 | 7.3 | 15.7 | |||
| NV | STRIDE n=161 | 0.74; 0.57–0.95 | 0.77; 0.59–1.00b | 18.0 | 57.1 | 2.1 | 13.2 |
| D n=163 | 0.82; 0.64–1.05 | 0.80; 0.62–1.03 | 19.0 | 56.4 | 3.7 | 13.8 | |
| S n=166 | 6.0 | 63.3 | 3.7 | 6.0 |
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
AstraZeneca.
Disclosure
L.S. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca, 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. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Eisai, Ipsen, Roche, Sirtex, Terumo, Incyte, Bayer; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, BMS, Incyte, AstraZeneca, Bayer, BMS, Boston Scientific, Roche, Sirtex; Financial Interests, Institutional, Research Grant: BMS, Sirtex; Financial Interests, Institutional, Invited Speaker: Adaptimmune; Non-Financial Interests, 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, AstraZeneca, Bayer, BMS, Eli Lilly, Exelixis, EMD Serono, Genentech/Roche, Merck, Merck, QED, Taiho, Novartis, Relay Therapeutics, Surface Oncology, LOXO Oncology; Financial Interests, Institutional, Research Grant: Partner Therapeutics; Non-Financial Interests, Advisory Role, IDMC chair and member: Genentech/Roche; Non-Financial Interests, Principal Investigator: Exelixis, 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, Sannofy, Mylan EPD, EA Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Teijin pharma, Servier Japan, Incy, Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Astellas, AstraZeneca, Incyte Japan; 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, Sanofy, Sumitomo Dainippon Bayer, Astellas, Incyte Japan. J. Park: Other, Personal and Institutional, Research Grant: Inno.N, Jeil Pharm; Financial Interests, Personal, Other, Consulting fees: AstraZeneca. BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD, ONO, Sanofi-Aventis, Servier, and TCUBEit. 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. 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: Other, Personal and Institutional, Other, Grant and research support: Amgen, AstraZeneca, Bristol Myers Squibb, MSD, Novartis, Pfizer, and Roche/Genentech. M.E. Reig Monzon: Financial Interests, Personal and Institutional, Other, Advisory Role , Invited Speaker and Research grant: Bayer; Financial Interests, Personal and Institutional, Other, Advisory Role and Invited Speaker: BMS, Roche, Lilly; Financial Interests, Personal, Other, Advisory Role, Research Grant: Ipsen; Financial Interests, Personal, Advisory Role: AstraZeneca, Universal DX; Financial Interests, Personal, Invited Speaker: Gilead, Eisai, BTG. M. Yarchoan: Financial Interests, Personal and Institutional, Advisory Role: Genentech; Financial Interests, Personal and Institutional, Research Grant, To John Hopkins: Genentec, Exelixis; Financial Interests, Institutional, Research Grant, To John Hopkins: Bristol-Myers Squibb, Incyte; Financial Interests, Personal and Institutional, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Role: Eisai, AstraZeneca, Replimune, Hepion. A.R. He: Other, Personal, Other, Advisory Board meeting on management of biliary cancer and HCC: AstraZeneca. 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, AstraZeneca, 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, AstraZeneca, BioNtech, BMS, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, Yiviva; Non-Financial Interests, Principal Investigator: AstraZeneca, Yiviva, QED. All other authors have declared no conflicts of interest.