Prof. Michel Ducreux of Gustave Roussy Cancer Center
near Paris presented the latest findings from the phase III IMbrave150 trial (NCT03434379),
which is evaluating atezolizumab plus bevacizumab (Avastin), a VEGF inhibitor that targets a
protein that promotes the development of blood vessels that supply tumours.
The study included 336 people with
unresectable (not removable by surgery) HCC who had not previously received
systemic treatment. Just under half had hepatitis B and about one in five had
hepatitis C. Three-quarters had cancer that had invaded the portal vein in the
liver or had spread elsewhere in the body (metastasis).
Participants were randomly assigned
to receive either intravenous infusions of atezolizumab plus bevacizumab
every three weeks or twice-daily oral sorafenib (Nexavar), a targeted therapy that has been considered the standard
Primary results recently published in the New England Journal of
Medicine showed that atezolizumab plus bevacizumab reduced
the risk of death by 42% compared with sorafenib. After a year on treatment,
overall survival rates were 67% and 55%, respectively, and the median
progression-free survival time was 6.8 versus 4.3 months, respectively.
At ILC, Ducreux presented detailed
safety results from the study, showing that although adverse event rates were roughly
similar in the two arms – almost everyone experienced some side effects – the types
of events differed.
Grade 3 or higher treatment-related adverse events
occurred in 36% of patients assigned to atezolizumab plus bevacizumab versus
46% of those who received sorafenib. While 16% and 10%, respectively,
discontinued treatment due to adverse events, temporary treatment interruption or
dose reduction to manage side effects occurred more often.
The most common treatment-related events in the atezolizumab
plus bevacizumab group were hypertension, protein in the urine, fatigue and
AST liver enzyme elevation. The leading events in the sorafenib group were hand
and foot syndrome (redness, swelling and pain on the
palms and soles of the feet), diarrhoea, decreased appetite and hypertension.
restores immune responses against cancer can also activate the immune system
more broadly, leading to excessive inflammation that can harm
organs throughout the body. Immune-mediated adverse events were more common in
the atezolizumab plus bevacizumab arm, and more people in that group
required management with corticosteroids.
Based on the strong efficacy results and
patient-reported outcomes, as well as the in-depth safety evaluation presented
here, the researchers concluded that atezolizumab plus bevacizumab
"should be considered a new standard of care" for people with advanced