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Daniele et al. Hepatoma Res 2021;7:61 https://dx.doi.org/10.20517/2394-5079.2021.58 Page 11 of 14

several investigators could have lost their equipoise regarding the study question.

However, unfortunately, the study question remains unanswered.

The two registered trials, Sharp and Asia Pacific, enrolled only a few dozen Child-Pugh B patients (overall
less than the BOOST study); therefore, in several countries, reimbursement of sorafenib is allowed only for
Child-Pugh A patients .
[10]
Retrospective, uncontrolled, and real life studies on the efficacy of sorafenib in HCC have been
reported [17-22] . The prospective observational phase 4 GIDEON trial was the largest one. It enrolled 3371
patients treated with sorafenib, including 666 Child-Pugh B and 74 Child-Pugh C cases. As expected,
survival was longer for Child-Pugh A patients compared to Child-Pugh B ones (13.6 months vs. 5.2 months,
respectively). Occurrence of serious adverse events (60% vs. 36%) and the rate of subsequent treatment
[21]
discontinuation (40% vs. 29%) were higher in Child-Pugh B than in Child-Pugh A patients .
A prospective, observational, multicenter study (INSIGHT) enrolled 791 patients treated with sorafenib in
daily practice conditions. In this trial, 182 (23%) Child-Pugh B patients were included. The median OS was
17.6, 8.1, and 5.6 months for Child-Pugh A, B, and C patients, respectively. In this study, adverse events
were less frequent among Child-Pugh B and C patients (50.8% and 30.8%, respectively) compared to Child-
Pugh A ones (72.4%), possibly due to the shorter duration of treatment .
[22]
In an Italian multicenter, open-label, phase 2 trial including Child-Pugh A (234 cases) and B patients (63
cases), median survival was shorter (3.8 months vs. 10.0 months) and the rate of adverse events was similar
or lower for Child-Pugh B compared to Child-Pugh A patients .
[20]
Overall, compliance and toxicity data reported in the small group of patients treated within the BOOST
study are consistent with other findings reported in the literature in the same setting.

[23]
Finally, McNamara et al. published a metanalysis of studies including HCC patients (both Child-Pugh A
and B) treated with sorafenib. The results regarding 1684 Child-Pugh B patients are similar to those of the
above-mentioned studies, with a worse prognosis than Child-Pugh A patients, due to their poorer liver
function, but no conclusions on the efficacy of sorafenib might be drawn in these patients.

Despite the limitations of the present study, due to failure in reaching the enrolment goal, BOOST
represents one of the few randomized lines of evidence available on the use of first-line sorafenib in Child-
Pugh B HCC patients. Very recently, the results of the PRODIGE 21 phase 2 trial were published, suggesting
a potential benefit of sorafenib in patients with HCC and Child-Pugh B liver cirrhosis with ALBI score
1/2 ; however, this needs to be confirmed prospectively. Similar results have been shown with
[24]
[25]
[26]
lenvatinibn , cabozantinib , and ramucirumab . Overall, these data suggest that a good baseline liver
[27]
function - as indicated by a lower ALBI score - is associated with a better outcome and a milder toxicity in
patients with advanced HCC treated with the above drugs.
We could not calculate ALBI scores for our patients since albumin and bilirubin values were collected as
categorical variables. Similar to what happened to our trial, Labeur et al. reported the premature
[28]
termination of a study aimed at personalizing sorafenib therapy in patients with HCC and Child-Pugh B7-8
liver function, assessing also sorafenib pharmacokinetics. However, only 5 out of the 45 planned patients
were actually recruited, over a period of almost three years.