The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: Final results of the START trial

Abstract

This phase II, investigator-initiated, prospective single-arm multinational study (ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin-based transarterial chemoembolization (TACE) in patients with intermediate-stage, unresectable hepatocellular carcinoma (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%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child-Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade 3 AEs were palmar-plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four 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 progression-free survival and time to progression were 384 and 415 days, respectively, and the estimated 3-year overall survival 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.

Transarterial chemoembolization plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review and meta-analysis

“…Causing approximate 700,000 deaths per year around the world, it is the third leading cause of cancer death and the fifth most common malignancy globally [1]. Furthermore, Asian countries contribute a large proportion of global HCC, making it a heavy burden in the Asia-Pacific region [2]. …”

“…Fortunately, as an inhibitor of many kinases, sorafenib can reduce proliferation and angiogenesis of tumour cells, increasing tumour apoptosis by inhibiting VEGF and PDGF receptors [7]. Therefore, combining sorafenib with TACE may be a promising strategy to reduce the recurrence rate of disease and improve the treatment efficacy compared to TACE mono-therapy [2]. …”

A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy

“…Attempts have been made to improve the efficacy of sorafenibbased HCC therapy by combining sorafenib, which may have low anti-HCC activity as a single agent, with other therapy regimens [12][13][14][15][16][17][18][19][20]. These coupled treatments are based on the assumption that the combination therapy, by targeting different signaling pathways, may have an additive or synergistic effect against tumors.…”

Management strategies for hepatocellular carcinoma: old certainties and new realities

“…Besides, the final results of the START trial, a phase II, investigator-initiated, prospective single-arm multinational study that evaluated sorafenib in combination with doxorubicin-based transarterial TACE in patients with intermediate-stage, unresectable HCC, evidenced that TACE/sorafenib cycles repeated every 6-8 weeks were well tolerated, 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, assessed by modified response evaluation criteria in solid tumors (RECIST). Median progression-free survival and time to progression were 384 and 415 days, respectively, and the estimated 3-year overall survival was 86.1 % [109].…”