Atezolizumab, Bevacizumab is First Combination to Reduce Risk of Cancer Recurrence in Some Forms of Early-Stage Liver Cancer

New findings from the pivotal phase 3 IMbrave050 trial investigating atezolizumab (Tecentriq, Genentech) plus bevacizumab (Avastin, Genentech) in patients with early-stage hepatocellular carcinoma (HCC) at high risk of disease recurrence has found that the trial met its primary endpoint of recurrence-free survival (RFS).

According to the trial, the combination showed a statistically significant improvement in RFS in the intent-to-treat population of patients with HCC who have an increased risk of recurrence following resection or ablation with curative intent, compared with active surveillance. Overall survival data were immature at the time of interim analysis and follow-up will continue to the next analysis.

Safety for the combination was consistent with the known safety profile for each therapeutic agent and with the underlying disease. Results from the trial will be shared with health authorities, including the FDA and European Medicines Agency, and presented at an upcoming medical meeting.

“Today, more than 70% of people with early-stage HCC may have their cancer return after surgery, which is associated with poorer prognosis and shorter survival,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development, in a press release. “IMbrave050 is the first phase 3 study to show that a cancer immunotherapy combination reduced the risk of disease returning in people with this type of HCC. We are excited by the clinical benefit that this adjuvant Tecentriq combination may bring to people with early liver cancer and look forward to seeing more mature data to further confirm the benefit.”

The IMbrave050 trial is a phase 3 global, multicenter, open-label, randomized study evaluating the efficacy and safety of atezolizumab plus bevacizumab compared with active surveillance in patients with HCC at high risk of recurrence, as determined by the size and number of cancerous lesions and the histopathology results, if available, after surgical resection or ablation with curative intent.

Investigators randomized 662 patients with a 1:1 ration to receive either atezolizumab 1200 mg every 3 weeks plus bevacizumab 15 mg/kg every 3 weeks for a maximum of 12 months, or no intervention with active surveillance. The primary endpoint is independent review facility-assessed RFS in patients with programmed death-ligand 1 (PD-L1)-positive disease.

Atezolizumab is a monoclonal antibody designed to bind with PD-L1, which is expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both programmed cell death protein-1 (PD-1) and B7.1 receptors. It has been approved for some of the most aggressive and difficult-to-treat forms of cancer, including a type of early-stage non-small cell lung cancer, small cell lung cancer, and HCC.

With liver cancer incidence increasing and mortality rates rising globally, effective treatments for this cancer are urgently needed. More than 900,000 individuals are diagnosed with the disease globally each year, which translates to 1 person diagnosed every 90 seconds.

Furthermore, 9 out of 10 cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol-related liver disease, and cirrhosis resulting from these conditions.

If diagnosed in early stages, surgery may be able to remove the primary tumor. However, an estimated 70% to 80% of patients with early-stage HCC experience disease recurrence following surgery. Early recurrence is associated with poorer prognosis and shorter survival. Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.

REFERENCE

Roche’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 3 trial. News release. Roche; January 19, 2023. Accessed January 23, 2023.