First Quarter 2008 - Issues in Hematology - ION Solutions

oncologistics drug updateNexavar ® in Unresectable HCC:New Treatment Option Basedon Significant Survival Benefitby: Ralph Boccia, M.D., F. A. C. P.Nexavar (sorafenib) is an oral multiple kinase inhibitorthat, as of November 2007, became the first systemictherapy approved by the U.S. Food and DrugAdministration (FDA) for patients with unresectablehepatocellular carcinoma (HCC), the most common formof liver cancer. As the only agent that has demonstrateda significant survival advantage in patients withunresectable HCC, Nexavar offers new hope for thisdifficult-to-treat disease. The HCC indication came within2 years of Nexavar’s approval for advanced renal cellcarcinoma (RCC)–for which the agent is now approved inmore than 60 countries.The incidence of HCC has been rising in the UnitedStates and globally. Current estimates are thatapproximately 19,000 new HCC cases are diagnosedannually in the United States. 1 The classic late diseasestage at diagnosis and the lack of effective systemictherapies have contributed to the dismal 8% 3-yearsurvival rate among patients with advanced disease. 2SHARP Results Move HCC to the Era ofTargeted TherapyFinal results of the international, double-blind, PhaseIII Sorafenib HCC Assessment Randomized Protocol(SHARP) trial, 3 which provided the basis for the FDA’sapproval of Nexavar in HCC, marked the first time anyagent has shown a survival advantage with predictableside effects in patients with unresectable HCC, and hasmoved HCC to the era of targeted therapy.The SHARP trial, reported at the 2007 annual meetingof the American Society of Clinical Oncology, enrolled602 patients recruited from centers in North and SouthAmerica, Europe, Australia, and New Zealand. 3Patients had histologically proven unresectable ormetastatic HCC, had not received previous systemictherapy, Eastern Cooperative Oncology Group(ECOG) performance status of 0-2, and lifeexpectancy of > 12 weeks. Patients could have receivedlocal therapy, including surgery, radiotherapy, hepaticarterial embolization, chemoembolization radiofrequencyablation, percutaneous ethanol injection, or cryoablation,as long as one target lesion had not been subjected tolocal therapy or a treated target lesion had increased insize by 25%. Patients were randomly assigned to receiveoral Nexavar tablets 400 mg twice daily (n=299) orplacebo tablets twice daily (n=303) dosed continuously.Primary study end points were overall survival (OS) andtime to symptom progression. Secondary end pointswere time to disease progression and disease controlrate, defined as complete or partial response or stabledisease for at least two treatment cycles.Baseline patient characteristics were similar in thetwo treatment groups. The median patient age wasapproximately 67 years, 87% were men, and 54% hadECOG performance status of 0. The majority of studyparticipants (> 95%) had Child-Pugh A liver functionstatus, approximately 82% had Barcelona Clinic LiverCancer (BCLC) stage C disease, and 70% had portalvein thrombosis.In February 2007, when 321 deaths had occurred(143 in the Nexavar arm, 178 in the placebo arm), thestudy was terminated early, after a prescheduled interimanalysis showed that the primary OS end pointoncologistics 2