The safety profile of durvalumab plus tremelimumab among those with unresectable hepatocellular carcinoma in the phase 3 HIMALAYA trial was comparable with the known profiles of each individual agent.
Combining durvalumab (Imfinzi) with tremelimumab (Imjudo) produced a clinically meaningful overall survival (OS) improvement at 4 years compared with sorafenib (Nexavar) among patients with unresectable hepatocellular carcinoma (HCC) who had not received previous systemic therapy, according to a press release on updated findings from the phase 3 HIMALAYA trial (NCT03298451).1
As of the updated analysis data cutoff date of January 23, 2023, the median OS was 16.4 months (95% CI, 14.2-19.6) among patients receiving the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen (n = 393) vs 13.8 months (95% CI, 12.3-16.1) among those receiving sorafenib (n = 389). Investigators reported that the experimental regimen reduced the risk of death by 22% vs the control arm (HR, 0.78; 95% CI, 0.67-0.92; P = .0037).
The 36-month OS rates in each treatment group were 30.7% vs 19.8%, and the 48-month OS rates were 25.2% vs 15.1%. The benefit of the STRIDE regimen was consistent across all relevant patient subgroups regardless of underlying disease cause or other baseline demographics, according to an ad-hoc exploratory analysis.
The median duration of follow-up in censored patients was 49.12 months (95% CI, 46.95-50.17) in the STRIDE group vs 47.31 months (95% CI, 45.08-49.15) in the sorafenib group.
The STRIDE regimen produced no new safety signals with longer follow-up in the HIMALAYA trial, and the safety profile was comparable with previous reports of each individual agent. Overall, 17.5% of patients receiving the STRIDE regimen and 9.6% of patients receiving sorafenib experienced grade 3/4 serious treatment-related adverse effects.
“Historically, only 7% of patients with advanced liver cancer have survived 5 years, making the HIMALAYA long-term survival data especially meaningful,” lead study investigator Bruno Sangro, MD, director of the Liver Unit and professor of Internal Medicine at Clínica Universidad de Navarra, Pamplona, Spain, said in the press release. “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.”
In the phase 3 HIMALAYA trial, 1324 patients were randomly assigned to receive 300 mg of tremelimumab plus 1500 mg of durvalumab every 4 weeks, 1500 mg of durvalumab alone every 4 weeks, 400 mg of sorafenib every day, or 75 mg of tremelimumab every 4 weeks for 4 doses plus durvalumab every 4 weeks.
The primary end point was OS. Secondary end points included progression-free survival, time to progression, objective response rate, disease control rate, and quality of life.
Patients 18 years and older with histopathological confirmation of HCC and no receipt of prior systemic therapy were eligible for enrollment on the trial. Additional inclusion criteria included having Barcelona Clinic Liver Cancer stage B or C disease, a Child-Pugh Score class of A, and an ECOG performance status of 0 or 1.
The FDA approved tremelimumab plus durvalumab for those with unresectable HCC in October 2022.2 In Japan, the Ministry of Health, Labour, and Welfare approved durvalumab plus tremelimumab for patients with unresectable HCC and those with advanced or recurrent non–small cell lung cancer in December 2022.3 Supporting data for both approvals in the HCC indications came from the HIMALAYA trial.
“In addition to this regimen demonstrating a favorable 3-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, [which are] important factors for patients with liver cancer who also have advanced liver disease,” principal investigator Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center, said in a press release at the time of the FDA approval.