Previously, the HIMALAYA study demonstrated that STRIDE (Single Tremelimumab Regular Interval Durvalumab regimen) significantly improved overall survival (OS) compared to sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). Recently published in Annals of Oncology, the 4-year updated results further support the long-term benefits of STRIDE in this patient population.
The phase III HIMALAYA study previously showed that STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) compared to sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). Additionally, durvalumab monotherapy exhibited noninferiority to sorafenib in terms of OS. This article presents the updated 4-year OS analysis of the study, providing further insights into the long-term efficacy outcomes of this treatment.
The phase III HIMALAYA trial enrolled participants with uHCC and no previous systemic treatment. In total, 1,171 patients were randomly assigned to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of the HIMALAYA study was to evaluate the superiority of STRIDE over sorafenib in terms of OS. In this updated analysis (data cut-off: 23 January 2023), OS and serious adverse events (AEs) were assessed after four years of follow-up. Additionally, baseline characteristics and subsequent therapies were analysed in long-term survivors (≥36 months beyond randomisation).
After a median follow-up of more than 47 months, a significant OS benefit was observed with STRIDE over sorafenib (HR[95%CI]: 0.78[0.67-0.92]). At 36 months, OS rates stood at 30.7% vs. 19.8% for STRIDE and sorafenib, respectively, and these were 25.2% vs. 15.1% at 48 months. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Of note, 57.3% of long-term survivors with STRIDE (n=103) did not need subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE since the primary analysis. Durvalumab maintained OS noninferiority to sorafenib, and no late-onset safety signals were identified.
These findings mark the most extensive follow-up period recorded in phase III studies conducted in uHCC to date. The remarkable 3- and 4-year OS rates further underscore the sustained long-term OS benefit of STRIDE compared to sorafenib. Notably, STRIDE exhibited a tolerable yet distinct safety profile compared to other uHCC therapies. These results continue to support the long-term benefits of STRIDE in a diverse patient population, mirroring the characteristics of uHCC patients worldwide.
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