947MO - Five-year overall survival (OS) and OS by tumour response measures from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC)

Background

In the phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved OS vs sorafenib 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). Here, we report the first 5-year OS analysis in uHCC and evaluate survival by multiple tumour response measures.

Methods

Participants (pts) with uHCC were randomised to STRIDE, durvalumab monotherapy or sorafenib. OS, 5-year OS rates, OS by disease control (DC), changes in tumour size and depth of response (DpR; Osgood et al. J Clin Oncol 2019) and serious adverse events (SAEs) were assessed. Extended long-term survivors were described. Data cut-off was 1 March 2024.

Results

The OS hazard ratio (HR) for STRIDE vs sorafenib was 0.76 (95% confidence interval [CI], 0.65–0.89) (Table). The 5-year OS rate was 19.6% with STRIDE vs 9.4% with sorafenib (rate ratio, 2.09) and was further improved in pts who achieved DC (28.7% vs 12.7%; rate ratio, 2.26). OS rates for pts who achieved ≥G2 (>25%) tumour shrinkage were 58.0% (57 pts at risk) vs 36.0% (8 pts at risk) at 48 months and 50.7% (34 pts at risk) vs 26.3% (4 pts at risk) at 60 months for STRIDE vs sorafenib, respectively. The rate of treatment-related SAEs with STRIDE did not change from the primary analysis. Table: 947MO

Conclusions

STRIDE demonstrated an unprecedented 5-year survival rate, with no additional serious safety events in the extended follow-up. The improved OS outcomes observed across multiple tumour response evaluations, including DC and DpR, provide novel insights on the clinical benefit of dual immune checkpoint inhibition beyond conventional measures of response. 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 Claire Tinderholm, PhD, CMC Connect, a division of IPG Health Medical Communications.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

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, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Zymeworks; 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; Non-Financial Interests, Leadership Role, Treasurer: ILCA; Non-Financial Interests, Leadership Role, Co-chair: EORTC GITCG HB/NET Task Force; Non-Financial Interests, Other, Special Expert Clinical Trials Europe: NCI HB Task Force. S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, 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, Other, Consultant fees: AstraZeneca. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. 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. Crysler: Financial Interests, Institutional, Research Funding: ACCRU, AstraZeneca/MedImmune, Bristol Myers Squibb, MedImmune. 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, Principal Investigator: MSD, BMS, Sirtex Medical, AstraZeneca. 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, Sanofi, Mylan EPD, EA Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Teijin pharma, Servier Japan, Incyte; Financial Interests, Personal, Advisory Board: Fuji film, Mundi 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, Advisory Role, IDMC chair and member: Genentech/Roche; Non-Financial Interests, Principal Investigator: Exelixis, AstraZeneca; Non-Financial Interests, Advisory Role, IDMC member: Merck. M.J. Paskow, D. Ran, A. Negro: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Makowsky: Financial Interests, Personal, Other, Former employee: 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, Pertzye, Servier; Non-Financial Interests, Principal Investigator: AstraZeneca, Yiviva, QED. All other authors have declared no conflicts of interest.