Original message:
This extended 4-year analysis of the phase III HIMALAYA study, conducted in patients with unresectable hepatocellular carcinoma, highlights the durable survival benefit associated with a single-dose tremelimumab regimen plus durvalumab at regular intervals (STRIDE regimen) compared with sorafenib. The 4-year overall survival rate improved significantly with STRIDE, reaching 25.2%, in contrast to 15.1% seen with sorafenib. Importantly, this prolonged survival benefit with STRIDE was consistent across multiple subgroups and showed additional improvement in patients who achieved disease control. Importantly, patients in the sorafenib group were more likely to undergo subsequent systemic cancer therapy than those in the Stride group.
The STRIDE regimen is emerging as a novel and effective treatment option, demonstrating a manageable safety profile as well as sustained long-term survival benefit over an extensive mean follow-up period of 4 years. These findings further strengthen the rationale for continued use of this regimen in patients battling unresectable hepatocellular carcinoma.
Summary
background
In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (UHCC), STRIDE (tremelimab regular interval durvalumab sol) significantly improved overall survival (OS) compared with sorafenib; Durvalumab monotherapy was noninferior to sorafenib for OS. The results reported here are from Himalaya’s updated four-year OS analysis.
Patients and methods
Participants with UHCC and no prior systemic therapy were randomly assigned to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The updated data cut-off date was January 23, 2023. OS and serious adverse events (AEs) were evaluated. Additionally, baseline characteristics and subsequent treatments in long-term survivors (36 months beyond randomization) were analyzed.
Result
For STRIDE, durvalumab, and sorafenib, the 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. The 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 OS rate at 48 months was higher for Stride at 25.2% compared to 15.1% for sorafenib. The long-term OS benefit of STRIDE was seen in all clinically relevant subgroups and further improved in participants who achieved disease control. Long-term survivors with STRIDE (n=103) included participants from all clinically relevant subgroups, and 57.3% (59/103) reported no subsequent anticancer therapy. No new serious AEs related to STRIDE treatment were observed from the primary analysis (17.5%; 68/388). Durvalumab maintained OS inferior to sorafenib and no late safety signals were identified.
conclusion
These data represent the longest follow-up to date in a Phase III study 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 but distinct safety profile from other current treatments for UHCC. The results continue to support the long-term benefits of STRIDE across diverse populations, mirroring UHCC globally.
waterfall:
B. Sangro, SL Chan, RK Kelly, A. Black, GK Abu-Alfa, et al.
DOI: https://doi.org/10.1016/j.annonc.2024.02.005
Link: https://www.annalsofoncology.org/article/S0923-7534(24)00049-8/fulltext