Abstract 167P
Background
STRIDE (Single T Regular Interval D) improved overall survival (OS) versus sorafenib (S) in uHCC overall and across HBV, HCV and other (no active viral hepatitis) aetiologies in the phase 3 HIMALAYA study (Sangro et al. Ann Oncol 2024). Non-viral uHCC aetiology prevalence is increasing worldwide. Thus, we aimed to further characterise the non-viral uHCC aetiology subgroup in HIMALAYA.
Methods
This exploratory analysis assessed STRIDE, D or S in participants (pts) with non-viral aetiology, here, more specifically defined as no active viral hepatitis or prior HBV infection. Self-reported alcohol use (yes [former/current] vs no [never]), history of metabolic/diabetes comorbidities, OS and safety were assessed. OS hazard ratios (HRs) and 95% CIs were calculated using a Cox proportional hazards model. Data cut-off was 23 Jan 2023.
Results
The non-viral subgroup included 388 pts randomised to STRIDE, D or S; 245 (63%) pts reported alcohol use (Table). Baseline characteristics were generally balanced across treatment arms. Non-viral aetiology and alcohol use were more common in Western countries than in Asia, per known trends. History of metabolic/diabetes comorbidities were observed in 147/245 (60%) pts with and 64/142 (45%) without alcohol use. OS was improved, and 36- and 48-mo OS rates were higher for STRIDE and D, versus S, in the non-viral subgroup. Grade 3/4 treatment-related adverse events were lower for STRIDE and D versus S in the non-viral subgroup (Table) and were consistent with previously reported rates. Table: 167P
| Non-viral aetiologyN=388 | |||
| STRIDE N=132 | D N=122 ∗ | S N=134 | |
| Alcohol use, n (%) Yes No | 88 (67) 44 (33) | 74 (61) 47 (39) | 83 (62) 51 (38) |
| Geographic region, n (%) Asia (excluding Japan) Alcohol use – Yes Rest of World (including Japan) Alcohol use – Yes | 15 (11) 8 (6) 117 (89) 80 (61) | 19 (16) 7 (6) 102 (84) 67 (55) | 17 (13) 10 (7) 117 (87) 73 (54) |
| OS HR (95% CI) vs S | 0.62 (0.47–0.81) | 0.69 (0.53–0.91) | |
| OS rates, % (95% CI) 36 mo 48 mo | 32 (24–40) 26 (18–34) | 26 (19–35) 20 (13–29) | 12 (7–18) 8 (4–14) |
| Grade 3/4 TRAEs, n/N (%) † | 42/129 (33) | 12/121 (10) | 54/131 (41) |
∗One pt with missing alcohol status was excluded from the yes/no alcohol use subsets.
†Percentages were calculated from the safety analysis set. TRAE, treatment-related adverse event.
Conclusions
STRIDE continued to demonstrate an OS benefit in a more strictly defined non-viral aetiology subgroup of pts. 36- and 48-mo OS rates remained higher in pts treated with STRIDE versus S, with no new safety signals observed. As rates of non-viral aetiology for HCC rise, these data further support the benefits of STRIDE in a diverse population consistent with uHCC globally.
Clinical trial identification
NCT0329845.
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
M.E. Reig Monzon: Financial Interests, Personal and Institutional, Other, Advisory Role; Invited Speaker; Travel Support; Principal Investigator; Educational Support: AstraZeneca, Roche; Financial Interests, Personal and Institutional, Other, Advisory Role; Invited Speaker; Travel Support; Principal Investigator; Research Grant; Educational support: Bayer; Financial Interests, Personal and Institutional, Other, Advisory Role; Invited Speaker; Travel Support; Educational Support: Eli Lilly, Ipsen; Financial Interests, Personal, Advisory Board: Geneos, Merck, Universal DX, Engitix Therapuetics; Financial Interests, Personal, Invited Speaker: Gilead, Guebert, Biotoscana Farma SA; Non-Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Nerviano, Incyte; Financial Interests, Personal and Institutional, Other, Principal Investigator; Educational Support: Boston Scientific; Financial Interests, Institutional, Other, Educational support: Eisai Merck MSD, Next; Financial Interests, Institutional, Other, Educational Support: Ciscar Medical, Eventy 03LLC (Egypt); Financial Interests, Institutional, Other, Principal Investigator; Educational Support: Terumo; Financial Interests, Personal and Institutional, Other, Advisory Role; Invited Speaker; Travel Support; Principal Investigator, Educational Support: BMS. V.C. Tam: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Eisai, Incyte, Ipsen, Merck, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Eisai; Financial Interests, Institutional, Invited Speaker: Exelixis, Incyte, Merck. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex, Terumo, Bayer, Adaptimmune; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, Incyte, AstraZeneca, Astellas Pharma, AstraZeneca, BMS, Boston Scientific, Roche; Financial Interests, Institutional, Research Grant: BMS, Sirtex. 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, Invited Speaker: Agios, Agios, AstraZeneca, AstraZeneca, Bayer, BMS, Eli Lilly, Exelixis, EMD Serono, Genentech/Roche, Merck, QED, Taiho, Novartis, Relay Therapeutics, Surface Oncology, Loxo Oncology, AstraZeneca, Merck, Servier, Compass, 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. 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. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. M.J. Paskow, C. Gupta, 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, Pertyze, Serview; Non-Financial Interests, Principal Investigator: AstraZeneca, Yiviva, QED. All other authors have declared no conflicts of interest.