1Division of Chemoradiotherapy, Cancer Center, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
This phase II, investigator-initiated, prospective single-arm multinational study (ClinicalTrials.gov registration NCT00990860), evaluated sorafenib in combination with doxorubicin-based TACE in patients with intermediate-stage, unresectable HCC. Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4-7 days after TACE). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib; and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), ECOG score 0 (81.8%), Child-Pugh A (91.8%) and BCLC stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well-tolerated, with only 8.1% of patients discontinuing due to AEs. The most common grade ≥3 AEs were palmar-plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). SAEs occurred in 52 patients during the study; however, only 4 were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median PFS and TTP were 384 days and 415 days, respectively, and the estimated 3-year OS was 86.1%. This study suggests that the combination of TACE and sorafenib is well-tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.