The European Commission has approved Tecentriq ( Atezolizumab ) in combination with Avastin ( Bevacizumab ) for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma ( HCC ) who have not received prior systemic therapy.
The approval is based on results from the phase III IMbrave150 study, which has shown that Atezolizumab in combination with Bevacizumab has reduced the risk of death ( overall survival [ OS ] ) by 42% ( hazard ratio [ HR ]=0.58; 95% CI: 0.42–0.79; p=0.0006 ) and has reduced the risk of disease worsening or death ( progression-free survival [ PFS ] ) by 41% ( HR=0.59; 95% CI: 0.47–0.76; p less than 0.0001 ), compared with Sorafenib.
IMbrave150 is the first phase III cancer immunotherapy study to show an improvement in both overall survival and progression-free survival in people with unresectable hepatocellular carcinoma compared with Sorafenib.
Grade 3–4 adverse events occurred in 57% of people receiving Atezolizumab and Bevacizumab and 55% of people receiving Sorafenib.
The most frequent serious adverse reactions for the combination ( 2% or more ) were bleeding in the gastrointestinal tract and fever.
These results were published in the New England Journal of Medicine ( 2020 ).
IMbrave150 is a global, multicentre, open-label study of 501 people with unresectable hepatocellular carcinoma who had not received prior systemic therapy.
People were randomised 2:1 to receive the combination of Atezolizumab and Bevacizumab or Sorafenib.
Atezolizumab was administered intravenously ( IV ), 1200mg on day 1 of each 21-day cycle, and Bevacizumab was administered IV, 15mg/kg on day 1 of each 21-day cycle.
Sorafenib was administered by mouth, 400mg twice per day, on days 1-21 of each 21-day cycle.
People received the combination or the control arm treatment until disease progression or unacceptable toxicity.
The two primary endpoints were overall survival and independent review facility ( IRF )-assessed progression-free survival per RECIST v1.1. Additional study endpoints included IRF-assessed overall response rate ( ORR ) per RECIST v1.1 and hepatocellular carcinoma mRECIST.
There is a strong scientific rationale to support the use of Atezolizumab plus Bevacizumab in combination.
The Atezolizumab and Bevacizumab regimen may enhance the potential of the immune system to combat a broad range of cancers.
Bevacizumab, in addition to its established anti-angiogenic effects, may further enhance Atezolizumab’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor ( VEGF )-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.
Hepatocellular carcinoma is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.
Every year, more than 750,000 people worldwide are diagnosed with hepatocellular carcinoma with the majority of cases in Asia and almost half of all cases in China.
In the US, the number of liver cancer cases have more than tripled since 1980 and hepatocellular carcinoma represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise, accounting for more than 80,000 diagnoses and approximately 77,000 deaths each year.
Hepatocellular carcinoma develops predominantly in people with cirrhosis due to chronic hepatitis ( B or C ) or alcohol consumption, and typically presents at an advanced stage.
The prognosis for unresectable hepatocellular carcinoma remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis. ( Xagena )
Source: Roche, 2020