Jens Ricke of Ludwig-Maximilians University in Munich, Germany, reported findings from
the Phase II SORAMIC trial, evaluating sorafenib plus selective internal
radiation therapy, or SIRT. The study was conducted in eleven European countries
This analysis looked at 424 participants with
locally advanced HCC in the palliative cohort of the study. They were not
considered suitable for potentially curative therapy and were instead assigned
to receive palliative care, which aims to improve symptoms but is not expected
to produce sustained remission or a cure.
This cohort included mostly men with a median
age of 66 years. Eighty per cent had cirrhosis. About 40% had liver disease
related to alcohol, about a quarter had hepatitis C and about 10% had hepatitis
B. Most were Child-Pugh Class A, meaning they had well-preserved liver
function, and BCLC Stage B or C. The median number of tumours was three and a
quarter had cancer metastasis outside the liver. They could have received prior
liver resection surgery or local therapies, but not external beam radiation
therapy. They were considered ineligible for transarterial chemoembolization
(TACE), though some had received it previously.
These participants were randomised to receive
either twice-daily sorafenib plus SIRT or sorafenib alone. SIRT was
administered using microspheres containing radioactive yttrium-90 injected into
arteries supplying the tumour. Actual treatment varied considerably in the
intention-to-treat population; a quarter of the people assigned to sorafenib
plus SIRT in fact received sorafenib alone, SIRT alone or no treatment.
Overall survival did not differ significantly
in the SIRT plus sorafenib and sorafenib only groups (median 12.1 vs 11.5
months, respectively). People who actually received SIRT plus sorafenib in the
per-protocol or as-treated population lived slightly longer (14.1 months), but
the difference still was not statistically significant.
Looking at various patient subgroups in the
per-protocol population, however, those under age 65, those without liver
cirrhosis and those without alcoholic liver disease appeared to do better with
SIRT plus sorafenib, Ricke reported.
Among the people without cirrhosis, median overall
survival was 22.2 months with the combination vs 9.9 months with sorafenib
alone. Among those without alcoholic liver disease, overall survival was 15.3
vs 11.1 months, respectively. Among those under age 65, it was 18.6 vs 11.3
months. Although the numbers were small, all these differences reached statistical
Treatment was generally safe but side-effects
were common. Diarrhoea was the most frequent adverse event in both groups,
reported by nearly half of people. Nearly 40% in both groups reported hand
and foot syndrome, or redness, swelling and pain on the palms and soles, a
known side-effect of sorafenib. Fatigue was more common in the SIRT plus sorafenib
group (35% vs 22%). Serious adverse events were rare in both groups and reported
quality of life was similar.
Going forward, Ricke said it will be important
to better define patient populations that might benefit from SIRT plus
sorafenib, such as those with good liver function. Most people with liver
cancer are older and have cirrhosis, but many people have liver disease related
to causes other than alcohol use.
"Although we were disappointed to
find no overall survival benefit of adding SIRT to sorafenib across the entire
study population, we did observe a survival benefit in younger patients, those
with a non-alcoholic aetiology of the cirrhosis, and those with no cirrhosis at
all," Ricke said in an EASL press release. "We believe our results
have generated some very interesting new hypotheses in terms of the types of
HCC patients that might benefit from combination therapy of SIRT and sorafenib,
and we hope to explore these further in the future."