Abstract 169P
Background
In the 4-year analysis of HIMALAYA, STRIDE (Single T Regular Interval D) sustained an overall survival (OS) benefit vs sorafenib (S) and showed further improvement in participants (pts) who achieved disease control (Sangro et al. Ann Oncol 2024). Cardiovascular (CV) and metabolic (MB) CMs are often found in people with HCC and can impact treatment options and outcomes. This exploratory analysis assessed outcomes in pts with CV or MB CMs in HIMALAYA.
Methods
CMs were based on medical history reported at baseline and qualified using preferred terms from CV or MB SMQs. Pts with >1 CM were counted once. OS by CMs was assessed in the full analysis set (FAS; pts randomised to STRIDE, D or S), including long-term survivors (LTS; pts alive ≥36 mo beyond randomisation). Within-arm OS HRs and 95% CIs were estimated using the unstratified Cox models. Safety was assessed in the safety analysis set (SAS; pts who received ≥1 dose of study drug). Data cut-off was 23 Jan 2023.
Results
Of the FAS, hypertension (HT) was the most common CV CM (STRIDE, 212 [54%]; D, 163 [42%]; S, 197 [51%]), and type 2 diabetes (T2DM) was the most common MB CM (STRIDE, 141 [36%]; D, 104 [27%]; S, 110 [28%]). In the STRIDE arm, OS HRs (95% CI) in pts with vs without CMs were 0.86 (0.68–1.08) for CV CMs and 1.16 (0.92–1.47) for MB CMs (Table). 36- and 48-mo OS rates were higher with STRIDE vs S in pts with CMs (Table). Higher proportions of pts with CMs were LTS with STRIDE vs S (Table). For STRIDE, rates of serious treatment-related adverse events (TRAEs) were similar in pts with CMs (21%) and all pts in the SAS (18%). Table: 169P
| STRIDEN=393 | DN=389 | SN=389 | ||||
| CV (n=216) | MB (n=159) | CV (n=172) | MB (n=130) | CV (n=207) | MB (n=135) | |
| OS HR (95% CI) in pts with vs without CMs | 0.86 (0.68–1.08) | 1.16 (0.92–1.47) | 0.98 (0.78–1.23) | 1.05 (0.83–1.33) | 0.93 (0.74–1.16) | 0.86 (0.68–1.08) |
| Landmark OS, % (95% CI) | ||||||
| 36-mo | 33 (27–39) | 26 (19–33) | 24 (18–31) | 22 (15–30) | 19 (14–24) | 21 (14–29) |
| 48-mo | 28 (22–34) | 20 (14–27) | 19 (13–25) | 16 (10–24) | 15 (10–21) | 16 (10–23) |
| LTS, n (%) | 61 (28) | 36 (23) | 33 (19) | 21 (16) | 34 (16) | 21 (16) |
| HT,* n/N (%) | 61/212 (29) | – | 32/163 (20) | – | 34/197 (17) | – |
| T2DM,† n/N (%) | – | 31/141 (22) | – | 17/104 (16) | – | 17/110 (15) |
| Serious TRAEs, n/N (%) ‡ | 45/215 (21) | 33/157 (21) | 12/172 (7) | 16/132 (12) | 19/201 (10) | 14/131 (11) |
Percent calculated of pts with *HT, † T2DM, or the ‡ SAS.
Conclusions
Pts with CMs experienced similar OS benefits from STRIDE as those without CMs, and long-term survival was achieved in more pts with STRIDE than S, irrespective of CM presence. No new safety signals were observed. Findings continue to support the unprecedented long-term benefits of STRIDE in a broad population reflective of uHCC globally.
Clinical trial identification
NCT03298451.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Eilidh McLachlan, PhD, 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
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, Invited Speaker: AstraZeneca, Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche, Servier, Agios, Eisai, FibroGen, Lilly, MSD, Roche, Servier; Financial Interests, Institutional, Invited Speaker, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Invited Speaker, 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. F. Dayyani: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca; Financial Interests, Personal, Invited Speaker: Ipsen, Sirtex, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, Bayer, Exelixis, Roche, Ipsen, Signatera, Merck, Taiho. 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. 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. 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. C.L. McCoy, 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.