Durvalumab Plus Tremelimumab Elicits Clinically Meaningful, 4-Year OS Advantage in Advanced HCC

Durvalumab plus a single priming dose of tremelimumab led to continued clinically meaningful overall survival benefit at 4 years compared with sorafenib in patients with previously untreated, unresectable hepatocellular carcinoma not eligible for localized therapy.

Durvalumab (Imfinzi) plus a single priming dose of tremelimumab (Imjudo; STRIDE) led to continued clinically meaningful overall survival (OS) benefit at 4 years compared with sorafenib (Nexavar) in patients with previously untreated, unresectable hepatocellular carcinoma (HCC) not eligible for localized therapy, according to updated data from the phase 3 HIMALAYA trial (NCT03298451).1

The estimated 4-year OS rate with the combination (n = 393) was 25.2% vs 15.1% with sorafenib (n = 389; HR, 0.78; 95% CI, 0.67-0.92; 2-sided P = .0037; 78% data maturity), showing similar magnitude of benefit from the 3-year landmark analysis, which revealed an OS rate of 30.7% with the combination and 19.8% with sorafenib alone. Median OS was 16.4 months (95% CI, 14.-2-19.6) and 13.8 months (95% CI, 12.3-16.1) with the combination and sorafenib, respectively.

Additionally, an ad-hoc exploratory analysis indicated that the benefit of the STRIDE regimen was consistent across all clinically relevant subgroups, including those surviving at least 3 years, regardless of the underlying disease cause (hepatitis B virus, hepatitis C virus, or nonviral) and other baseline demographics.

“Historically, only 7% of patients with advanced liver cancer have survived 5 years, making the HIMALAYA long-term survival data especially meaningful. One in 4 patients treated with the STRIDE regimen were still alive at 4 years, reinforcing this novel regimen as a standard of care in this setting,” Bruno Sangro, MD, PhD, director of the Liver Unit and professor of Internal Medicine at Clínica Universidad de Navarra, Pamplona, Spain, said in a press release.

On October 21, 2022, the FDA approved the combination for adult patients with unresectable HCC based on an earlier analysis of HIMALAYA which showed improved OS, progression-free survival (PFS), and objective response rate (ORR) with the combination.2

The randomized, open-label, multicenter, global phase 3 trial evaluated durvalumab alone and at a dose of 1500 mg in combination with a single priming dose of 300 mg of tremelimumab, followed by durvalumab every 4 weeks, vs sorafenib.

A total of 1324 patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy were randomly assigned to the STRIDE regimen, durvalumab monotherapy, or sorafenib monotherapy.

The primary end point of the study was OS for the combination vs sorafenib, and key secondary end points included OS for durvalumab vs sorafenib, ORR, and PFS for the combination and for durvalumab alone.

At the time of the updated analysis, the median duration of follow-up in censored patients was 49.12 months (95% CI, 46.95-50.17) for the combination and 47.31 months (95% CI, 45.08-49.15) for sorafenib, at which time 291 (74.0%) and 316 (81.2%) survival events had been reported, respectively.

The safety profile of the STRIDE regimen was consistent with the known profiles of each agent alone, and no new safety signals were observed with extended follow-up. Serious treatment-related adverse effects (TRAEs), including grade 3, 4, and 5 events, occurred in 17.5% of patients treated with the STRIDE regimen vs 9.6% of patients treated with sorafenib. Notably, no new serious TRAEs occurred after the primary analysis with the combination.

“The remarkable 4-year survival benefit shown with [durvalumab] and [tremelimumab] in this advanced liver cancer setting supports the use of the STRIDE regimen to treat a broad, eligible patient population globally. These latest results from HIMALAYA are part of a series of clinical trials aiming to deliver innovative treatments for patients at different stages of liver cancer,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said.

References

  1. Imfinzi plus Imjudo demonstrated sustained overall survival benefit in advanced liver cancer with an unprecedented one in four patients alive at four years in HIMALAYA Phase III trial. News release. AstraZeneca. June 29, 2023. Accessed June 30, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-plus-imjudo-demonstrated-sustained-overall-survival-benefit-in-the-himalaya-phase-iii-trial.html
  2. FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. News release. FDA. October 21, 2022. Accessed June 30, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma