Sunitinib malate in patients with advanced hepatocellular carcinoma (HCC) who progressed under therapy with sorafenib

Aims: For patients (pts) with advanced HCC who progressed under therapy with sorafenib, no established second-line therapy exists. Three phase II studies have investigated the safety and efficacy of sunitinib malate, another multityrosine kinase inhibitor targeting VEGFR-1,-2,-3, PDGFR-α, -ß, KIT, FLT3 and RET, as first-line therapy in advanced HCC. Based on promising data from the sequential use of both drugs in renal cell carcinoma, we treated pts with advanced HCC and progression under sorafenib treatment with sunitinib (off label-use). Methods: From January to October 2008, 9 pts were treated with 37.5mg sunitinib per day (4 weeks on, 2 weeks off, every 6 weeks) regardless of liver function, tumor stage or history of liver allograft. Adverse events (AEs) were assessed using CTCAE v3.0, tumor response was assessed according to RECIST. Results: 7 pts presented with liver cirrhosis (LCI) Child-Pugh A or without LCI and 1/1 pt had LCI Child-Pugh B/C, respectively. BCLC stage was C/D in 8/1 pts and ECOG performance status was 0/1/2 in 2/5/2 pts. All pts had distant metastases (lung, adrenal gland, peritoneum and brain). Most common AEs noted across all dose levels were dysgeusia, bleeding, nausea, diarrhea, leukopenia and fatigue. Most AEs were grade I/II in severity and manageable with symptomatic treatment. However, a dose modification was necessary in 1 pt and therapy was discontinued in 3 pts due to variceal or cerebral hemorrhages. 2 pts achieved radiological stable disease after 3–4 months. 7 pts had no radiological follow-up due to significantly clinical deterioration or shortage of follow-up period. Conclusions: Sunitinib may be a treatment option in pts with advanced HCC who progressed under therapy with sorafenib but remaining in sufficiently good clinical condition. However, a treatment-related hemorrhage could not be ruled out in a subgroup of pts.

Literatur: Zhu AX et al., A phase II study of sunitinib in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol, suppl., 2007; 25: abstract 4637 Faivre SJ et al., Assessment of safety and drug-induced tumor necrosis with sunitinib in patients with unresectable HCC, J Clin Oncol, suppl., 2007; 25: abstract 3546 Hoda D et al., Phase II study of sunitinib malate in adult patients with metastatic or surgically unresctable hepatocellular carcinoma. J Clin Oncol, suppl. 2008; abstract 267

HCC - sorafenib - sunitinib