Imfinzi Plus Imjudo Shows Significant Five-Year Survival Improvement in Unresectable Liver Cancer

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Updated data from the Phase III HIMALAYA trial (NCT03298451) show the combination of Imfinzi (durvalumab) plus Imjudo (tremelimumab) produced an unprecedented improvement to five-year overall survival (OS) rates compared to sorafenib in patients with unresectable hepatocellular carcinoma (uHCC).^1-3 In the exploratory analysis, investigators found that adding a single priming dose of Imjudo to Imfinzi lowered the risk of death by 24% vs. sorafenib (based on a hazard ratio [HR] of 0.76; 95% confidence interval [CI] 0.65-0.89). Results from the trial, published by the Annals of Oncology, show an estimated 19.6% of patients administered Imfinzi plus Imjudo were alive at five years compared to 9.4% of patients administered sorafenib.

“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,” lead HIMALAYA investigator Lorenza Rimassa, MD, associate professor of Medical Oncology, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy, said in a press release. “These data reinforce the use of this novel dual immunotherapy regimen and are an important milestone for patients with this devastating disease.”¹

Imfinzi is selective, high-affinity human IgG1 monoclonal antibody that attaches to PD-L1 and blocks interactions with PD-1 and CD80 on activated T cells. Current FDA-approved indications for Imfinzi include for the treatment of unresectable, stage III non-small cell lung cancer (NSCLC) in patients with disease that has not progressed following chemoradiation therapy; for the treatment of ES-SCLC; combined with a limited course of Imjudo (tremelimumab) and chemotherapy to treat metastatic NSCLC; in combination with gemcitabine plus cisplatin to treat locally advanced or metastatic biliary tract cancer; and in combination with Imjudo to treat unresectable hepatocellular carcinoma. Additionally, the drug was approved last month in combination with chemotherapy for adult patients with resectable early-stage (IIA-IIIB) NSCLC without EGFR mutations or ALK rearrangements.⁴

The study authors noted that up until 2020, first-line uHCC treatment was limited to sorafenib and lenvatinib, both of which are tyrosine kinase inhibitors. Immune checkpoint inhibitor (ICI)-based combination therapies, such as Imfinzi plus Imjudo—also called STRIDE (Single Tremelimumab Regular Interval Durvalumab)—as well as atezolizumab plus bevacizumab, and camrelizumab plus rivoceranib, have produced significant improvements in OS compared with sorafenib. As such, the STRIDE regimen is increasingly gaining momentum globally as a first-line treatment for uHCC, according to the study authors.³

“It is remarkable to see nearly 20% of patients with advanced liver cancer treated with the STRIDE regimen alive at five years compared to only about 7% of patients living that long historically,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in a press release. “This is a major step forward, setting a new survival benchmark. This underscores our commitment to following patients for the long term to help us better characterize the enduring clinical benefits of this innovative priming approach with an anti-CTLA-4 antibody added to PD-L1 blockade.”¹

The randomized, open-label, multicenter, global HIMALAYA trial evaluated Imfinzi monotherapy and a regimen consisting of a single priming dose of Imjudo 300 mg added to Imfinzi 1500 mg followed by Imfinzi every four weeks (STRIDE regimen) compared with sorafenib. Investigators enrolled 1,324 patients with unresectable, advanced HCC who did not receive prior treatment with systemic therapy and were not eligible for locoregional therapy. The trial’s primary endpoint was OS for the combination compared with sorafenib, with key secondary endpoints that included OS for Imfinzi versus sorafenib, objective response rate, and progression-free survival for the combination and for Imfinzi monotherapy.

A subgroup analysis of patients who achieved disease control, which was defined as either complete or partial response or stable disease, found that 28.7% of patients administered the STRIDE regimen were alive at five years compared with 12.7% of patients administered sorafenib. Further, an exploratory analysis of depth of response found that more patients administered the STRIDE regimen achieved deep responses that produced longer survival vs. sorafenib.

“Reaching the five-year survival milestone is both clinically significant and emotionally meaningful for people with advanced liver cancer and their families,” said Sarah Manes, Liver Cancers Program director at Global Liver Institute, in a press release. “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.”¹

References

1. Imfinzi plus Imjudo demonstrated unprecedented overall survival in advanced liver cancer with one in five patients surviving five years in HIMALAYA Phase III trial. News release. AstraZeneca. Published September 16, 2024. Accessed September 16, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-plus-imjudo-demonstrated-unprecedented-overall-survival-alc-with-one-in-five-patients-surviving-five-years-himalaya-phase-iii-trial.html

2. Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma (HIMALAYA). ClinicalTrials.gov. August 30, 2024. Accessed September 16, 2024. https://clinicaltrials.gov/study/NCT03298451

3. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Sangro, B.Azevedo, Sergio et al. Annals of Oncology, Volume 35, Issue 5, 448-457.

4. Imfinzi approved in the US for the treatment of resectable non-small cell lung cancer before and after surgery. AstraZeneca. August 16, 2024. Accessed September 16, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-us-for-resectable-lung-cancer.html