Adjuvant treatment with the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) was demonstrated to delay cancer recurrence when compared to active surveillance (no additional treatment) in patients with early-stage hepatocellular carcinoma (HCC) at high risk of disease recurrence, according to the results of the recently published phase 3 IMbrave050 clinical trial (NCT04102098), unfortunately longer term follow failed to confirm an overall survival benefit.1,3
Liver cancer is the most common cancer worldwide and each year in the United States, more than 28,000 people are diagnosed with primary liver cancer. Long-term survival with liver cancer remains poor, but recent advances in surgery, other liver-directed therapies, and systemic immunotherapy drug combinations are all contributing to improved outcomes. In addition, advances in supportive care have made liver cancer treatment more tolerable, leading to improved quality of life.
Currently more than 70% of people with early-stage HCC experience a cancer recurrence following treatment with surgery alone. Researchers have been evaluating drug combinations to administer after surgery in order to determine if the high rate of cancer recurrence following surgery can be reduced. Treatment with the immunotherapy combination of Tecentriq and Avastin was established as the standard of care for individuals with more advanced HCC in 2020 because it delays cancer recurrence and prolongs survival.2 The IMbrave050 clinical trial evaluated the same combination in patients with HCC at high risk of recurrence, following surgical resection or ablation with curative intent.
Study findings, which were initially presented at the 2023 AACR Annual Meeting, showed that with a median follow-up of 17.4 months, the 12-month survival rate without recurrence was improved to 78% for the Tecentriq-Avastin combination compared with 63% for those not receiving the combination.3
IMbrave050 investigators enrolled patients with a confirmed first diagnosis of HCC who had undergone curative-intent resection or ablation, were free of disease, had Child-Pugh class A disease, and an ECOG performance status of 0 or 1.
To be eligible for enrollment, patients were required to meet the following criteria for high risk of disease recurrence:
- Resection and up to 3 tumors with the largest tumor greater than 5 cm irrespective of vascular invasion or poor tumor differentiation defined as grade 3 or 4;
- Resection and 4 or more tumors with the largest tumor being up to 5 cm regardless of vascular invasion or poor tumor differentiation.
- Resection and up to 3 tumors with the largest tumor up to 5 cm with vascular invasion and/or poor differentiation.
- Ablation and 1 tumor greater than 2 cm but not greater than 5 cm
- Ablation and several tumors but no greater than 4 tumors, all up to 5 cm
Serious side effects occurred in 24% of individuals who received Tecentriq-Avastin compared with only vs 10% of those who had active surveillance.
This initial trial results were hoped to be practice-changing for patients with high-risk HCC but the longer follow up failing to show survival benefit has been disappointing. It is more likely that combined therapy using local treatments such as TACE or TEAR in combination with chemo-immunotherapy could provide improved outcomes. This approach is being evaluated in the Emerald and other clinical trials.
Patients not included in the trial were those with fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC; evidence of residual, or individuals with recurrent, or metastatic disease.
References
- Genentech’s Tecentriq plus Avastin is the first treatment combination to reduce the risk of cancer returning in people with certain types of early-stage liver cancer in a phase III trial. News release. Genentech. January 18, 2023. Accessed January 19, 2023. http://bit.ly/3R5XvLX
- FDA approves Genentech’s Tecentriq in combination with Avastin for people with the most common form of liver cancer. News release. Genentech. May 29, 2020. Accessed January 19, 2023. https://bit.ly/2Aneztc
- Chow P, Chen M, Cheng A-L, et al. IMbrave050: phase 3 study of adjuvant atezolizumab + bevacizumab versus active surveillance in patients with hepatocellular carcinoma at high risk of disease recurrence following resection or ablation. Presented at: 2023 AACR Annual Meeting; April 14-19, 2023; Orlando, Florida. Abstract CT003.
- Cheng A-L, Qin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862-873. doi:10.1016/j.jhep.2021.11.030
