HIMALAYA: Long-term OS benefit with STRIDE regimen in uHCC

Treatment with tremelimumab plus durvalumab (STRIDE* regimen) continues to yield overall survival (OS) benefit at 4 years among patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib, according to the updated results of the HIMALAYA trial presented at ESMO WCGIC 2023.

At an extended follow-up of 4 years, patients who received the STRIDE regimen achieved a 22-percent reduction in the risk of death as opposed to those who were treated with sorafenib (hazard ratio [HR], 0.78; two-sided p=0.0037), which was consistent with the primary analysis. [ESMO WCGIC 2023, abstract SO-15]

Moreover, the 48-month OS rate was higher among those treated with STRIDE than those on sorafenib (25.2 percent vs 15.1 percent), with a longer median OS of 16.4 months for STRIDE vs 13.8 months for sorafenib.

At 36 months, STRIDE-treated patients also achieved a higher OS rate compared with the sorafenib recipients (24.7 percent vs 19.8 percent).

With regard to response, disease control rate was 60.1 percent in the STRIDE arm and 60.7 percent in the sorafenib arm. However, those who achieved disease control with STRIDE had better OS rates at 3 years (44.6 percent vs 27.9 percent) and 4 years (36.2 percent vs 20.3 percent) than with sorafenib. “I believe this is an intriguing biologic issue, but more importantly, it has a clinical impact,” said lead author Dr Bruno Sangro from the Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain.

“These results reinforce the sustained, long-term OS benefit of STRIDE vs sorafenib … and STRIDE demonstrated unprecedented 3- and 4-year survival data, with one in four patients alive at 4 years,” Sangro said.

The phase III HIMALAYA trial included 1,171 patients with uHCC who were randomized to receive the STRIDE regimen comprising one dose of tremelimumab 300 mg plus durvalumab 1,500 mg Q4W (n=393), durvalumab monotherapy (n=389), or sorafenib 400 mg BID (n=389). The primary objective of the study was to evaluate the OS and safety of STRIDE or durvalumab monotherapy vs sorafenib.

Durvalumab monotherapy demonstrated noninferiority over sorafenib in terms of the OS rate at 4 years (19.3 percent vs 15.1 percent), with a longer median OS (16.6 vs 13.8 months; HR 0.86). These findings were consistent with that observed in the primary analysis.

In terms of safety, no new serious treatment-related adverse events occurred after the primary analysis for STRIDE (17.5 percent for both the primary and updated analyses).

“The STRIDE regimen maintained a tolerable and differentiated safety profile from other current uHCC therapies,” noted Sangro.

“This 4-year updated analysis of the phase III HIMALAYA study presents the longest follow-up to date in phase III studies in uHCC,” Sangro stated. “STRIDE showed a [long-term OS] benefit vs sorafenib that was not driven by any particular subgroup of patients and that [also] occurred regardless of response.”