Scientific publications

Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

Feb 19, 2024 | Magazine: Annals of Oncology

B Sangro  1 , S L Chan  2 , R K Kelley  3 , G Lau  4 , M Kudo  5 , W Sukeepaisarnjaroen  6 , M Yarchoan  7 , E N De Toni  8 , J Furuse  9 , Y K Kang  10 , P R Galle  11 , L Rimassa  12 , A Heurgué  13 , V C Tam  14 , T Van Dao  15 , S C Thungappa  16 , V Breder  17 , Y Ostapenko  18 , M Reig  19 , M Makowsky  20 , M J Paskow  21 , C Gupta  22 , J F Kurland  20 , A Negro  20 , G K Abou-Alfa  23 ; HIMALAYA investigators

Background: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a four-year updated OS analysis of HIMALAYA.

Patients and methods: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The updated data cut-off was January 23, 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization).

Results: For STRIDE, durvalumab, and sorafenib, median (95% CI) follow-up was 49.12 (46.95-50.17), 48.46 (46.82-49.81), and 47.31 (45.08-49.15) months, respectively. OS HR (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n=103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late onset safety signals were identified.

Conclusions: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented three- and four-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.

CITATION  Ann Oncol. 2024 Feb 19:S0923-7534(24)00049-8.  doi: 10.1016/j.annonc.2024.02.005