A multicenter Phase II study of sorafenib in Japanese patients with advanced hepatocellular carcinoma and Child Pugh A and B class

Abstract

This study shows sorafenib has similar effectiveness in the recent post-approval studies and is well-tolerated in Japanese pts with HCC and Child Pugh A class. Sorafenib should be used with great care for Child Pugh class B pts.

Systematic Literature Review of Trials Assessing Recommended Systemic Treatments in Hepatocellular Carcinoma

“…Finally, 57 records (representing 50 trials) were included in the SLR. These 50 trials included 34 trials in the 1L setting (six single arm [30][31][32][33][34][35], six RCTs comparing against a recommended treatment or placebo [36][37][38][39][40][41][42][43], one trial with both single arm and randomized groups [44], and 26 RCTs comparing against a non-recommended treatment ) and 11 trials in the 2L setting (five single arm [71][72][73][74][75][76], five RCTs comparing against placebo [77][78][79][80][81][82], and one trial with both single arm and randomized groups [83][84][85][86]).…”

“…In terms of study design (Supplementary Table 9), blinding varied among the RCTs; most of the 1L RCTs were open label, but all the 2L RCTs were double blind. The majority of trials (18 of 24) were Phase II or Phase III, and half the trials (12 of 24) were global (i.e., included patients from countries within and not within the Asia-Pacific region); however, three trials included patients from outside Asia-Pacific countries [30,36,76] and nine trials included patients exclusively from Asia-Pacific countries [31][32][33][34][35]37,38,71,72]. Nine of the 12 global trials (i.e., CELESTIAL, CheckMate 040, GO30140, IMbrave150, KEYNOTE-240, REFLECT, REACH, REACH-2, RESORCE) provided subgroup analyses for patients from the Asia-Pacific region in the original publication or in separate analyses [87][88][89][90][91][92][93][94].…”

“…Inclusion criteria for general disease characteristics, such as the ECOG performance status, BCLC stage, and Child-Pugh class, were largely similar within the trials (Supplementary Table 10); however, some studies allowed patients with more advanced disease stage to enroll. These included four trials that allowed patients with ECOG performance status of 2 to enroll (including early trials for sorafenib) [35][36][37][38] and six trials that allowed patients with Child-Pugh class B to enroll [30,31,35,38,44,76]. Notably, all 2L RCTs had highly similar general inclusion criteria regarding ECOG performance status of 0 or 1, BCLC stage B or C, and Child-Pugh class A; patients with more severe disease were excluded from 2L RCTs.…”

“…Reporting of AFP was heterogeneous, hindering the review of similarity; three trials reported the proportion of patients with AFP ≥200 ng/ml [34,74,81]; nine trials reported the proportion of patients with AFP ≥400 ng/ml [32,42,44,72,[76][77][78][79]83]; six reported mean or median values for the cohort [33,36,39,71,78,80]; two reported only the proportion with levels greater than the upper limit of detection [30,37]; six trials provided no indication of AFP [31,35,38,40,73,86]. Two studies required AFP >400 ng/ml for inclusion [76,80].…”

The Efficacy of Surgery in Advanced Hepatocellular Carcinoma: A Cohort Study

“…Previous studies documented that advanced HCC patients with lymph nodes invasion or metastases had median survival times of 6-8 months [20,21]. However, the same group of patients treated with molecular targeted drugs, surgery alone, or a combination of both therapies could expect longer survival times of 7.0-20.4 months [7,[22][23][24][25]. In these analyses, the combination of surgery with molecular targeted drugs or with another surgery often resulted in longer mOS.…”