Updated data from the Phase III HIMALAYA trial reveal that the combination of Imfinzi (durvalumab) and Imjudo (tremelimumab) has produced an unprecedented improvement in five-year overall survival (OS) rates compared to sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). The exploratory analysis indicated that adding a single priming dose of Imjudo to Imfinzi lowered the risk of death by 24% compared to sorafenib (HR 0.76; 95% CI: 0.65-0.89). The results, published in the Annals of Oncology, showed an estimated 19.6% of patients administered Imfinzi plus Imjudo were alive at five years, compared to 9.4% of patients administered sorafenib.
Significant Survival Advantage
According to Dr. Lorenza Rimassa, lead HIMALAYA investigator and associate professor of Medical Oncology at Humanitas University, "Treatment with Imfinzi plus Imjudo for patients with advanced liver cancer doubled the overall survival rate at five years, a significant survival advantage over sorafenib that has also become even more pronounced over time." She emphasized that these data reinforce the use of this novel dual immunotherapy regimen and represent an important milestone for patients with this devastating disease.
Mechanism of Action and Current Approvals
Imfinzi is a selective, high-affinity human IgG1 monoclonal antibody that binds to PD-L1, blocking its interactions with PD-1 and CD80 on activated T cells. It is currently FDA-approved for unresectable, stage III non-small cell lung cancer (NSCLC), ES-SCLC, metastatic NSCLC (in combination with Imjudo and chemotherapy), locally advanced or metastatic biliary tract cancer (in combination with gemcitabine plus cisplatin), and unresectable hepatocellular carcinoma (in combination with Imjudo). Recently, it was also approved with chemotherapy for resectable early-stage NSCLC without EGFR mutations or ALK rearrangements.
Evolving Treatment Landscape
Prior to 2020, first-line uHCC treatment was primarily limited to sorafenib and lenvatinib, both tyrosine kinase inhibitors. However, immune checkpoint inhibitor (ICI)-based combination therapies, such as Imfinzi plus Imjudo (STRIDE regimen), atezolizumab plus bevacizumab, and camrelizumab plus rivoceranib, have demonstrated significant improvements in OS compared to sorafenib. The STRIDE regimen is increasingly recognized as a first-line treatment for uHCC globally.
HIMALAYA Trial Details
The randomized, open-label, multicenter, global HIMALAYA trial evaluated Imfinzi monotherapy and the STRIDE regimen (single priming dose of Imjudo 300 mg added to Imfinzi 1500 mg, followed by Imfinzi every four weeks) against sorafenib. The trial enrolled 1,324 patients with unresectable, advanced HCC who had not received prior systemic therapy and were ineligible for locoregional therapy. The primary endpoint was OS for the combination versus sorafenib, with key secondary endpoints including OS for Imfinzi versus sorafenib, objective response rate, and progression-free survival for both the combination and Imfinzi monotherapy.
Outcomes and Exploratory Analysis
A subgroup analysis of patients achieving disease control (complete or partial response, or stable disease) showed that 28.7% of those administered the STRIDE regimen were alive at five years, compared to 12.7% on sorafenib. Exploratory analysis of depth of response indicated that more patients on the STRIDE regimen achieved deep responses, leading to longer survival compared to sorafenib.
Hope for Patients
Sarah Manes, Liver Cancers Program director at Global Liver Institute, stated, "Reaching the five-year survival milestone is both clinically significant and emotionally meaningful for people with advanced liver cancer and their families. We are thrilled to see this progress in improving outcomes with new treatment options, bringing new hope for long-term survivorship to patients in our community."
