Pokuri VK, et al. - Researchers assessed the safety/efficacy of a rationally designed combination of sunitinib and transarterial chemoembolization (TACE) in inoperable hepatocellular carcinoma (HCC) patients with Child-Pugh A disease. Biomarkers for this combination therapy were also explored. Treatment with sunitinib and TACE combination provided encouraging progression-free survival and overall survival with acceptable toxicity. Moreover, combination therapy offered increased benefit as demonstrated by potential imaging and serum biomarkers.

• Researchers administered 37.5 mg sunitinib from days 1 to 7 followed by TACE on day 8 in inoperable HCC patients with Child-Pugh A disease.
• Resumption of sunitinib from days 15 to 36, was followed by 2 weeks off.
• Patients received subsequent sunitinib cycles of 4 weeks on and 2 weeks off.
• Evaluation of dynamic contrast-enhanced magnetic resonance imaging and circulating soluble biomarkers at baseline, day 8, day 10, and day 36 was carried out.

• This study included a total of 16 patients with liver only (n=10) and extrahepatic disease (n=6).
• For a clinical benefit rate of 81%, 2 partial responses, 11 stable disease, and 3 clinical deteriorations were seen after a median follow-up of 12.8 months.
• Median progression-free survival (PFS) of 8 months (95% CI, 4.3-9.3) and overall survival of 14.9 months (95% CI, 6.3-27.1) was reported.
• Sunitinib-induced grade 3/4 toxicities were seen in 11 of 16 patients (69%), the most frequent being thrombocytopenia, amylase/lipase elevations, lymphopenia, and fatigue.
• Researchers noted that mean K^trans(volume transfer constant) and viable tumor percent in consented patients decreased by 27% and 14.8%, respectively, with combination therapy.
• Combination therapy brought about decrease in soluble vascular endothelial growth factor receptor-2 (sVEGFR2) levels, cytokines (interleukin-8, interleukin-21), and monocytes.
• In addition, it was noted that estimated sunitinib IC50 values of 15 and 10 ng/mL modulated K^trans and AUC90.
• With K^trans and AUC90, decline in sVEGFR2 levels was noted.