127O - Five-year overall survival (OS) and OS by baseline liver function from the phase III HIMALAYA study of tremelimumab (T) plus durvalumab (D) in unresectable hepatocellular carcinoma (uHCC)

Background

In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single T Regular Interval D) significantly improved OS versus sorafenib (S) in the primary analysis (Abou-Alfa et al. NEJM Evid 2022) and demonstrated durable long-term survival with a 4-year OS rate of 25.2% (Sangro et al. Ann Oncol 2024). Albumin-bilirubin (ALBI) grade is an objective measure of liver function in HCC. Here, we report a 5-year OS analysis in uHCC and evaluate OS by baseline ALBI grade.

Methods

Participants (pts) were randomised to STRIDE, D or S. OS, the proportion of extended long-term survivors (eLTS; alive ≥48 months) and serious adverse events (SAEs) were assessed in all pts or in subgroups of pts stratified by baseline ALBI grade (1 [score ≤-2.60] vs 2/3 [score >-2.60 to ≤-1.39/score >-1.39]). The data cut-off was 1 March 2024.

Results

The OS hazard ratio (HR) for STRIDE versus S was 0.76 (95% CI, 0.65–0.89; Table). The 5-year OS rate was 19.6% with STRIDE versus 9.4% with S (rate ratio, 2.09). In ALBI grade 1 pts, OS HR was 0.79 (95% CI, 0.63–0.99) for STRIDE versus S, and the 5-year OS rate was 24.3% with STRIDE versus 13.6% with S. In ALBI grade 2/3 pts, OS HR was 0.79 (95% CI, 0.63–1.00) for STRIDE versus S, and the 5-year OS rate was 13.7% with STRIDE versus 4.7% with S. Data for D are shown in the table. In ALBI grade 1 versus 2/3 pts, 57/217 (26.3%) versus 26/175 (14.9%) were eLTS with STRIDE, and 36/203 (17.7%) versus 9/186 (4.8%) were eLTS with S. Rates of treatment-related SAEs with STRIDE did not change from the primary analysis for either ALBI subgroup (Table) Table: 127O

*ALBI grade data not available for one pt.

Conclusions

STRIDE demonstrated an unprecedented 5-year survival rate, with no additional serious safety events observed, and long-term OS benefit over S in a diverse population of pts with uHCC regardless of baseline liver function. These results set a new benchmark in uHCC, with one in five pts alive with STRIDE at 5 years.

Clinical trial identification

NCT03298451.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Jennifer Stewart, PhD, MBA, on behalf of CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Esai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AbbVie, AstraZeneca, Basilea, Bayer, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Guerbet, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Zymeworks, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche, Servier; Financial Interests, Institutional, Coordinating PI, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Local PI: Agios, Eisai, Fibrogen, Lilly, MSD, Roche, Servier; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Coordinating PI, European PI: AstraZeneca, TransThera Sciences, Taiho Oncology; Non-Financial Interests, Personal, Leadership Role, Treasurer: ILCA; Non-Financial Interests, Personal, Leadership Role, Chair: EORTC GITCG HPB/NET Task Force; Non-Financial Interests, Personal, Other, Special Expert Clinical Trials Europe: NCI HB Task Force. S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, Astra-Zeneca, MSD, Roche; Financial Interests, Personal, Invited Speaker: Astra-Zeneca, MSD, Eisai, Roche, IPSEN; Financial Interests, Personal, Research Grant: Eisai, MSD. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche. G. Lau: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. V.V. Breder: Financial Interests, Personal, Advisory Board, payment for lectures: Roche, AstraZeneca, Eisai, Bayer, Novartis. M. Varela: Financial Interests, Personal, Advisory Board: Boston, Roche, Eisai-MSD, AstraZeneca. O.V. Crysler: Financial Interests, Institutional, Local PI, Local PI , research funding paid to institution: AstraZeneca, MedImmune, Bristol Myers Squibb, Takeda Pharmaceutical Company. M. Bouattour: Financial Interests, Personal, Advisory Board: MSD, BMS, SIRTEX Medical, IPSEN, AbbVie, AstraZeneca, Servier, Taiho; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Principal Investigator: MSD, BMS, SIRTEX Medical, AstraZeneca. V.T. Dao: Financial Interests, Personal, Other, Consultant fees: AstraZeneca, Bayer, Eisai, IPSEN, MSD, Novartis, Pfizer, Pierre Faber, Roche, and Taiho Pharmaceutical. A. Faccio: Financial Interests, Personal, Invited Speaker: 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; 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, Sanofi, Sumitomo Dainippon Bayer, Astellas, Incyte Japan; Financial Interests, Personal, Steering Committee Member: Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Astellas, AstraZeneca, Incyte Japan. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. 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, Personal, Advisory Board, Ad Board late 2022: Regeneron; Financial Interests, Personal, Advisory Board, GI ASCO 2023 Ad Board: Tyra Biosciences; Financial Interests, Personal, Advisory Board, Ad board around GI ASCO 2023: Compass Therapeutics; Financial Interests, Institutional, Steering Committee Member: Agios, AstraZeneca, Merck; Financial Interests, Institutional, Local PI: Agios, AstraZeneca, BMS, Eli Lilly, EMD Serono, Genentech/Roche, Merck, QED, Taiho, Novartis, Relay Therapeutics, Surface Oncology, Loxo Oncology, Compass; Financial Interests, Institutional, Coordinating PI: Bayer, Exelixis, AstraZeneca, Merck, Servier, Tyra Biosciences; 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, AstraZeneca; Non-Financial Interests, Personal, Advisory Role, IDMC member: Merck. M.J. Paskow: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. M. Makowsky: Financial Interests, Personal, Other, Former employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. D. Ran, 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: AstraZeneca, Autem, Berry Genomics, Boehringer Ingelheim, Eisai, Exelixis, Genentech/Roche, Incyte, Ipsen, Merck, Novartis, Servier, Vector, Yiviva, AbbVie, BioNTech, BMS, Merus, Tempus; 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, Genentech/Roche, Puma, QED, Yiviva, Agenus, Elicio, Helsinn, Parker Institute, Pertyze, Serview; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Yiviva, QED. All other authors have declared no conflicts of interest.