- Medical Updates

The phase III IMbrave150 study, evaluating Atezolizumab ( Tecentriq ) in combination with Bevacizumab ( Avastin ) as a treatment for people with unresectable hepatocellular carcinoma ( HCC ) who have not received prior systemic therapy, met both of its co-primary endpoints demonstrating statistically significant and clinically meaningful improvements in overall survival ( OS ) and progression-free survival ( PFS ) compared with standard-of-care Sorafenib ( Nexavar ).

Safety for the combination of Atezolizumab and Bevacizumab was consistent with the known safety profiles of the individual medicines, with no new safety signals identified.

IMbrave150 is a global phase III, multicentre, open-label study of 501 people with unresectable hepatocellular carcinoma who have not received prior systemic therapy.
People were randomised 2:1 to receive the combination of Atezolizumab and Bevacizumab or Sorafenib.
Atezolizumab was administered intravenously, 1200 mg on day 1 of each 21-day cycle, and Bevacizumab was administered intravenously, 15 mg/kg on day 1 of each 21-day cycle.
Sorafenib was administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle.
People received the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Co-primary endpoints were overall survival ( OS ) and progression-free survival ( PFS ) by independent-review facility (IRF) per RECIST v1.1. Secondary efficacy endpoints included overall response rate ( ORR ), time to progression ( TTP ) and duration of response ( DOR ), as measured by RECIST v1.1 ( investigator-assessed [ INV ] and IRF ) and HCC mRECIST ( IRF ), as well as patient-reported outcomes ( PROs ), safety and pharmacokinetics.

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 carcinom is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.
The disease affects over 750,000 people every year,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 HCC represents the fastest rising cause of cancer-related death.
HCC 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 HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis. ( Xagena )

Source: Roche, 2019