781TiP - Phase II study of everolimus and capecitabine in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Results of the first 1...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anticancer agents
Hepatobiliary Cancers
Biological Therapy
Presenter S.A.C. Luelmo
Authors S.A.C. Luelmo1, S. Osanto2, N. Weijl3
  • 1Leiden University Medical Center (LUMC), 2300RC - Leiden/NL
  • 2Clinical Oncology, Leiden University Medical Center (LUMC), NL-2300 RC - Leiden/NL
  • 3Internal Medicine, Leiden University Medical Center (LUMC), Leiden/NL



Sorafenib is currently the only standard systemic treatment for patients with HCC. Capecitabine is one of the few chemotherapeutic agents which have demonstrated activity in patients with metastatic HCC. The PI3K-AKT-mTOR pathway plays a key role in HCC development. We investigated a combination of everolimus, an m-TOR inhibitor, and capecitabine.


Patients with histologically confirmed locally advanced (n = 4) or metastatic (n = 6) HCC with measurable disease who were progressive on or intolerant to sorafenib were included. Child Pugh A (n = 7) and Child Pugh B (n = 3) liver cirrhosis was accepted. Patients were treated with everolimus 2 dd 3.0 mg continuously. After a 2 week period capecitabine 2 dd 500 mg/m2 was added on a 2 week on, 1 week off schedule.


10 patients have been included of whom 2 patients are still on treatment. Of the 10 patients 7 patients were evaluable for response: best response was stable disease in 4 patients and progressive disease in 3 patients. The median progression free survival (PFS) was 3.6 months (2.7-18.5 months) for 1st line sorafenib and 3.4 months (1.3-14.7 months) for 2nd line treatment with everolimus/capecitabine. The patients who had the longest treatment on sorafenib tended to be the patients who had longer 2nd line treatment with the exception of one patient who stopped everolimus and capecitabine due to progression of liver cirrhosis. The treatment was generally well tolerated. Three patients had dose modifications due to toxicity: one for grade 2 thrombocytopenia which was partly due to underlying livercirrhosis, one for grade 2 painful mucositis of the anus and one for grade 3 oral mucositis.


The combination of everolimus and capecitabine has a reasonable toxicity profile and may show significant activity in patients with advanced HCC pretreated with sorafenib. This combination therapy warrants further investigation as a possible second line treatment for selected patients with HCC.


All authors have declared no conflicts of interest.