Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma Journal Article
| Authors: | Sangro, B.; Chan, S. L.; Kelley, R. K.; Lau, G.; Kudo, M.; Sukeepaisarnjaroen, W.; Yarchoan, M.; De Toni, E. N.; Furuse, J.; Kang, Y. K.; Galle, P. R.; Rimassa, L.; Heurgué, A.; Tam, V. C.; Van Dao, T.; Thungappa, S. C.; Breder, V.; Ostapenko, Y.; Reig, M.; Makowsky, M.; Paskow, M. J.; Gupta, C.; Kurland, J. F.; Negro, A.; Abou-Alfa, G. K.; for the HIMALAYA investigators |
| Article Title: | Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma |
| Abstract: | 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 4-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 23 January 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% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (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 3- and 4-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. © 2024 The Author(s) |
| Keywords: | adult; controlled study; aged; middle aged; survival analysis; survival rate; major clinical study; overall survival; clinical feature; clinical trial; drug tolerability; mortality; sorafenib; drug safety; liver cell carcinoma; carcinoma, hepatocellular; liver neoplasms; follow up; antineoplastic agent; ticilimumab; infection; heart disease; kidney disease; randomized controlled trial; antineoplastic combined chemotherapy protocols; pathology; cancer therapy; cancer survivor; monoclonal antibody; antibodies, monoclonal; adverse outcome; multicenter study; liver tumor; data analysis; mental disease; skin disease; phase 3 clinical trial; eye disease; general condition improvement; connective tissue disease; disease control; hepatobiliary disease; metabolic disorder; thorax disease; musculoskeletal disease; endocrine disease; immunopathology; polyp; injury; drug use; hematologic disease; vascular disease; respiratory tract disease; cyst; study design; tremelimumab; drug intoxication; urinary tract disease; immune checkpoint inhibitor; antibodies, monoclonal, humanized; mediastinum disease; nutritional disorder; humans; human; male; female; article; durvalumab; unresectable hepatocellular carcinoma |
| Journal Title: | Annals of Oncology |
| Volume: | 35 |
| Issue: | 5 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-05-01 |
| Start Page: | 448 |
| End Page: | 457 |
| Language: | English |
| DOI: | 10.1016/j.annonc.2024.02.005 |
| PUBMED: | 38382875 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
