IO Learning spoke with Riccardo Lencioni, MD, FSIR, EBIR, regarding the trial design for the EMERALD-1 study, which was recently presented at the Symposium for Clinical Interventional Oncology (CIO) and was designated as a “CIO Best Poster.”
Can you share some background on your study?
Hepatocellular carcinoma (HCC) accounts for more than 80% of all primary liver cancer diagnoses worldwide. Patients with HCC are often not candidates for curative treatments, because they are diagnosed at advanced stages of the disease. In patients with intermediate stage or locoregional disease, survival benefits are offered by transarterial chemoembolization, or TACE, which is the standard of care. To date, no systemic treatment options have provided an additional benefit above locoregional treatment for this patient population. Because of this, there remains a significant unmet medical need for new, effective therapies for patients with locoregional HCC.
What sets your study apart?
EMERALD-1 is the first phase III trial to examine a checkpoint inhibitor, with or without a vascular endothelial growth factor (VEGF) inhibitor, in combination with TACE therapy in HCC. A checkpoint inhibitor (± VEGF inhibitor) + TACE strategy for locoregional HCC is supported by recent studies of combination treatment with immune checkpoint and VEGF inhibitors for advanced stage HCC that resulted in improved progression-free survival and overall survival. Because EMERALD-1 is also the first phase III trial in intermediate HCC, this study will advance our knowledge of effective treatments for this patient population.
Can you describe your study protocol?
The study includes adult patients with histologically or radiologically confirmed HCC that is not amenable to curative therapy and who have not received prior systemic therapy for HCC. Patients are required to have a Child-Pugh score A to B7, and an Eastern Cooperative Oncology Group performance status of 0 or 1.
Approximately 600 patients will be randomized 1:1:1 to receive durvalumab + TACE followed by durvalumab, durvalumab + TACE followed by durvalumab + bevacizumab, or TACE alone.
The primary endpoint is progression-free survival. Key secondary endpoints include safety, overall survival, time to progression, objective response rate, duration of response, and disease control rate. Health-related quality of life will also be evaluated.
Why did you choose this methodology?
TACE is the most well-studied locoregional therapy for intermediate HCC and is accepted as the standard of care for these patients. Emerging evidence suggests that TACE can prime the immune system to target tumor cells. Combining TACE with a checkpoint inhibitor may enhance anti-tumor immune responses by blocking cancer cells’ ability to suppress anti-tumor immune activity. TACE is also known to increase VEGF expression, and the addition of a VEGF inhibitor to this combination can reduce revascularization in the tumor after TACE therapy.
In our study, up to 4-5 TACE treatments can be administered to the patient prior to beginning with combination therapy. This allows us to test the ability of durvalumab with or without bevacizumab to extend the efficacy of TACE treatments and promote improved survival, delay in disease progression, and durability of response.
How might your findings eventually affect clinical practice?
If this trial meets its primary endpoint of improved progression-free survival, the combination of TACE + durvalumab, followed by durvalumab with or without bevacizumab, could become a new standard of care for this patient population who are in need of new, effective treatment options.
What are you hoping that attendees take away from your presentation?
We have designed this trial to understand if priming the immune system with TACE, while removing the immune blockade with durvalumab and inhibiting VEGF signaling, can improve efficacy over TACE alone in patients with intermediate HCC. We are hoping to garner interest in this treatment approach and invite physicians involved in the clinical management of HCC to enroll patients to answer this important question.
Title: Transarterial Chemoembolization Combined With Durvalumab ± Bevacizumab in Patients With Locoregional HCC (EMERALD-1).
Authors: Riccardo Lencioni, University of Pisa School of Medicine, Pisa, Italy; Masatoshi Kudo, Kindai University, Osaka, Japan; Shukui Qin, Cancer Center of Nanjing, Jinling Hospital, Nanjing, China; Zhenggang Ren, Zhongshan Hospital, Fudan University, Shanghai, China; Stephen Chan, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong; Joseph Erinjeri, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Yasuaki Arai, National Cancer Center, Tokyo, Japan; Philip He, AstraZeneca, Gaithersburg, MD, USA; Shethah Morgan, AstraZeneca, Cambridge, United Kingdom; Gordon Cohen, AstraZeneca, Gaithersburg, MD, USA; Bruno Sangro, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
Presented at CIO 2020 on October 27, 2020.
To inquire about enrolling patients in this study, please contact Gordon Cohen at AstraZeneca. Email: firstname.lastname@example.org
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