Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related deaths globally and in Korea. Many patients diagnosed at advanced stage, and systemic therapy is mainstay of treatment in patients with advanced HCC. However, immune-checkpoint inhibitor (ICI) monotherapy did not significantly improve overall survival in phase III studies. According to previous retrospective analyses, ICI treatment in advanced HCC showed different organ-specific responses. The intrahepatic HCC was the least responsive organ to ICI treatment. The failure of phase III trials of ICI monotherapy may have been attributed to different organ-specific response pattern of ICIs. Combination of atezolizumab plus bevacizumab is expected to overcome the immunosuppressive microenvironment of liver and may enhance intrahepatic response of ICI.
In a previous retrospective analysis of pembrolizumab treated patients with advanced melanoma and NSCLC, patients with liver metastases showed poorer PFS compared with those without liver metastases with reduced ORR. Similar observations have also been reported in metastatic of triple-negative breast cancer patients, there were no responses in patients with liver metastases. Taken together the results of previous studies, hepatic metastases had reduced response to ICI compared with metastases at other organs, regardless of cancer types. In addition, ICI treatment in advanced HCC showed different organ-specific responses. The poorer response rate in liver to ICI might be affected by liver-specific immunosuppressive microenvironment (TME). To overcome the unfavorable immunosuppressive TME of the liver, combination strategies are needed to achieve enhanced anti-tumor immune responses or alleviated tumor-associated immunosuppression. Since the cause of death in most HCC patients was hepatic failure due to intrahepatic HCC or underlying liver cirrhosis, the response rate to ICI of intrahepatic tumor lesions is a crucial factor in determining the overall prognosis of advanced HCC. Therefore, we hypothesize that combination strategy of atezolizumab plus bevacizumab may increase organ specific response in patients with advanced HCC, and may improve survival outcomes accordingly. Objectives We hypothesize that combination strategy of atezolizumab plus bevacizumab may increase organ specific response in patients with advanced HCC, and may improve survival outcomes accordingly.
Study Type
OBSERVATIONAL
Enrollment
131
Patients received combination therapy with atezolizumab (Tecentriq) and bevacizumab (Avastin) as first-line systemic treatment for advanced hepatocellular carcinoma.
Cha Medical Center
Seongnam-si, Gyeonggi-do, South Korea
Percentage of Lesions With Organ-specific Response
Organ-specific response will be assessed at the lesion level according to RECIST 1.1 criteria. Up to two target lesions per organ (maximum of five total lesions per patient) will be selected and measured unidimensionally. Complete response (CR) is defined as disappearance of the lesion or lymph node short axis diameter \<1.0 cm. Partial response (PR) is defined as ≥30% reduction in lesion size. Progressive disease (PD) is defined as ≥20% increase in lesion size. Stable disease (SD) is defined as neither CR, PR, nor PD. New lesions are recorded in addition to original target lesions to determine the total tumor burden.
Time frame: From treatment initiation until last follow-up (median 10.1 months)
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