Charalampos Floudas and colleagues from the US National Cancer Institute
evaluated a combination of durvalumab and tremelimumab in 10 people with HCC and 12
with biliary tract cancers that could not be surgically removed or treated
A majority of participants were men and the median age was 63 years.
Seven of the liver cancer patients had hepatitis C and one had hepatitis B;
most had compensated liver disease. A quarter had cancer that had spread beyond
the liver or biliary tract. They had previously tried (or been offered and
refused) at least one prior therapy.
Participants were treated with durvalumab plus tremelimumab for four
monthly cycles, followed by once-monthly durvalumab monotherapy until disease
progression or unacceptable toxicity. CT scans were performed every eight weeks
to monitor disease progression.
Two people with liver cancer (20%) and one person with biliary tract cancer
(8.3%) achieved partial responses; there were no complete responses. Five people with HCC (50%) and five people with biliary tract cancer (41.7%) had stable disease, meaning
they neither improved nor worsened. Adding these numbers together, the disease
control rate was 70% for HCC and 50% for biliary tract cancer.
In the liver cancer group, the median progression-free survival, meaning
patients were still alive without worsening of disease, was 7.8 months and the
median overall survival was 15.9 months. The biliary tract cancer group fared worse, with
a median progression-free survival of 3.1 months and a median overall survival
of 5.45 months.
These findings for the people with HCC compare favourably to the response
rate of around 20%, stable
disease rate of around 35% and median overall survival of about 15 months for
previously treated people in the CheckMate
040 study of nivolumab for HCC. In that
study, survival was substantially longer for treatment-naive patients. Overall
survival has generally been shorter in studies of targeted therapies such as
sorafenib (Nexavar) or lenvatinib (Lenvima).
"Combined immune checkpoint inhibition with Imfinzi and
tremelimumab "is well tolerated and demonstrates promising activity in
patients with advanced HCC and BTC," the researchers concluded.
This study did not include a comparison group taking durvalumab alone,
so it is unclear how much tremelimumab contributed to efficacy. This question
will be addressed in the phase 3 HIMALAYA trial, in which people with liver
cancer will be randomised to receive durvalumab alone, sorafenib alone or one
of two regimens combining durvalumab and tremelimumab.