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Atezolizumab associated with Bevacizumab improves overall survival and progression-free survival in people with unresectable hepatocellular carcinoma compared with Sorafenib

Results from the phase III IMbrave150 study evaluating Atezolizumab ( Tecentriq ) in combination with Bevacizumab ( Avastin ) were presented.
The data have shown statistically significant and clinically meaningful improvements in overall survival ( OS ) and progression-free survival ( PFS ), compared with Sorafenib ( Nexavar ), in people with unresectable hepatocellular carcinoma ( HCC ) who have not received prior systemic therapy.

Atezolizumab in combination with Bevacizumab has reduced the risk of death ( 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 ( PFS ) by 41% ( HR=0.59; 95% CI: 0.47–0.76; p less than 0.0001 ), compared with Sorafenib.
Safety for Atezolizumab and Bevacizumab was consistent with the known safety profiles of the individual medicines.

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 ( IV ), 1200 mg on day 1 of each 21-day cycle, and Bevacizumab was administered IV, 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 have 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 OS and PFS by independent review facility ( IRF ) per Response Evaluation Criteria in Solid Tumours Version 1.1 ( RECIST v1.1 ).
Additional study 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 ( including time to deterioration of patient-reported quality of life ), safety and pharmacokinetics.

Grade 3-4 adverse events occurred in 57% of people receiving Atezolizumab and Bevacizumab and 55% of people receiving Sorafenib.
Grade 5 adverse effects occurred in 5% and 6% of people, respectively.

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.
Over 750,000 people worldwide are diagnosed with hepatocellular carcinoma 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 hepatocellular carcinoma represents the fastest rising cause of cancer-related death, while in Europe liver cancer is also on the rise.
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, 2019