P-0087 Safety and Tolerability of Sorafenib in Child-Pugh B Patients with Hepatocellular Carcinoma: a Single Center Experience

Abstract Introduction Sorafenib is a Tyrosine Kinase Inhibitor approved for the treatment of advanced hepatocellular cancer (HCC). The phase III trial, which led to the approval of sorafenib accrued most patients with Child-Pugh score of A. There is very little data on safety and tolerability of the drug in patients with more advanced Child-Pugh score of B who have a good performance status. This study was undertaken to study the same at our institution. Methods John H Stroger Jr. Hospital of Cook County caters to the underserved and uninsured population of Chicago, USA. All patients who were prescribed sorafenib since 2007 were identified from pharmacy database. All charts were retrospectively reviewed. Patients with HCC, Child-Pugh score 7-9 (B), good performance status (ECOG 0-2), ineligible for liver transplant that had documentation of taking sorafenib were included. Patients with incomplete data or who were non-compliant or eligible for chemoembolization at the time of initiating sorafenib were excluded. A note was made of development of adverse events (AEs), timing of AEs and changes made to the sorafenib dosage, if any. Results A total 72 patients were prescribed sorafenib of which 25 had Child-Pugh B HCC and received sorafenib. Nine patients were excluded based on above criteria and 16 were included in the study. There were 13 (81%) men and 3 (19%) women. Average age was 54 years. Adverse events any grade happened in all patients (100%). Only 5 (31%) patients had tolerable AEs and were able to continue full dose sorafenib while 11 (69%) required a dose reduction or discontinuation due to AEs. Eight patients (50%) discontinued the drug of which 6 had worsening liver function and one each with grade 4 diarrhea and hemorrhage. All 8 required hospitalization for management of AEs. Seven patients (44%) developed grade 2 or more diarrhea while 5 (31%) developed moderate to severe mucocutaneous toxicities. Worsening liver dysfunction happened in 6 (38%) and hemorrhage in 4 patients (2 with grade 2 epistaxis and 2 with grade 4 lower gastrointestinal hemorrhage). 11 of the 16 patients (69%) developed AEs within 4 weeks of initiating sorafenib with 83% of worsening liver dysfunction happening within 1 month. Dividing by actual Child-Pugh Score, 50% of patients with score of 7 were able to continue sorafenib with tolerable AEs while only 20% were able to continue if the score was 8-9. Average age of patients who were able to continue sorafenib was 48 years compared to 57 years for ones who had it discontinued or dose reduced. Conclusion Patients with HCC and Child-Pugh score B, despite good performance status; do not tolerate sorafenib very well with a high incidence of AEs. However carefully selected patients with a younger age and lower score of 7 on Child-Pugh scale are able to tolerate the drug with acceptable toxicity suggesting a role of sorafenib in this subgroup of Child-Pugh B patients. Also majority of patients develop AEs within the first few weeks of initiation of the drug, suggesting close monitoring of these patients after sorafenib initiation.