Advanced Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma, atezolizumab, bevacizumab
Brief summary
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.
Detailed description
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.
Interventions
Patients received combination therapy with atezolizumab (Tecentriq) and bevacizumab (Avastin) as first-line systemic treatment for advanced hepatocellular carcinoma.
Sponsors
Hoffmann-La Roche
CHA University
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed HCC pathological or non-invasive assessment according to American Association for the Study of Liver Diseases (AASLD) criteria * ECOG performance status 0 or 1 * Patients who received Atezolizumab and Bevacizumab combination therapy as first-line systemic treatment for unresectable HCC * Barcelona Clinic Liver Cancer (BCLC) stage B or C * Child-Pugh class A * Measurable lesion * Adequate hematologic and organ function
Exclusion criteria
* History of autoimmune disease * Concomitant anticoagulation at therapeutic doses. Low dose aspirin for * cardio protection is permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Lesions With Organ-specific Response | From treatment initiation until last follow-up (median 10.1 months) | 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. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atezolizumab Plus Bevacizumab Atezolizumab plus bevacizumab
Atezolizumab plus bevacizumab: Atezolizumab plus bevacizumab | 131 |
| Total | 131 |
Baseline characteristics
| Characteristic | Atezolizumab Plus Bevacizumab |
|---|---|
| Age, Continuous Age | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 131 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Hong Kong | 7 participants |
| Region of Enrollment South Korea | 124 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 57 / 131 |
| other Total, other adverse events | 108 / 131 |
| serious Total, serious adverse events | 16 / 131 |
Outcome results
Primary
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)
Population: Organ-specific responses were assessed for 260 individual tumor lesions from 131 participants who received atezolizumab plus bevacizumab: 152 liver lesions, 42 lymph node lesions, 24 lung lesions, and 42 other metastatic lesions were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atezolizumab Plus Bevacizumab | Percentage of Lesions With Organ-specific Response | ORR for 260 individual tumor lesions | 29.8 Percentage of Units (lesions) |
| Atezolizumab Plus Bevacizumab | Percentage of Lesions With Organ-specific Response | ORR for 152 liver lesions | 28.3 Percentage of Units (lesions) |
| Atezolizumab Plus Bevacizumab | Percentage of Lesions With Organ-specific Response | ORR for 42 LNs lesions | 40.5 Percentage of Units (lesions) |
| Atezolizumab Plus Bevacizumab | Percentage of Lesions With Organ-specific Response | ORR for 24 lungs lesions | 29.1 Percentage of Units (lesions) |
| Atezolizumab Plus Bevacizumab | Percentage of Lesions With Organ-specific Response | ORR for other metastatic lesions | 19.0 Percentage of Units (lesions) |