GHP July 2017

26 GHP / July 2017 NEWS , “For a decade, there has been no advance in the first-line systemic treatment of unresectable hepatocellular carcinoma in Europe,” said Professor Jeff Evans, Professor of Translational Cancer Research, University of Glasgow. “There is a significant unmet need for patients with this advanced form of liver cancer, where treatment options are limited.” The EMA submission is based on results of the pivotal Phase III REFLECT study (Study 304). Lenvatinib was the only first-line agent to demonstrate non-inferior overall survival (OS) versus sorafenib in uHCC, with a significant and clinically meaningful improvement versus sorafenib in all secondary efficacy endpoints of progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR). The REFLECT study results were presented in an oral session at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago and will be published soon in the peer-reviewed journal The Lancet. “This announcement represents another important milestone for lenvatinib in difficult-to-treat cancer types,” said Gary Hendler, Chairman & CEO EMEA, Chief 1612GH13 First-Line Systemic Unresectable Hepatocellular Carcinoma Treatment On July26, Eisai announced it has submittedamarketing authorisationapplication to the EuropeanMedicinesAgency (EMA) for thefirst-lineuse of lenvatinib inpatientswithunresectable hepatocellular carcinoma (uHCC). Patientswithhepatocellular carcinoma face apoor prognosis, witha complexdiseasewhichaccounts for approximately90%of liver cancer casesworldwide. Commercial Officer, Oncology Business Group at Eisai. “Based on the results observed in the REFLECT trial we are looking forward to working with the EMA to bring a much-needed first-line new treatment option for liver cancer patients in Europe one step closer.” Lenvatinib is currently approved in the EU for the treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI). Lenvatinib is also approved in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor (VEGF)-targeted therapy. Eisai is dedicated to the discovery, development and production of innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai’s human health care (hhc) mission, which strives to better understand the needs of patients and their families to increase the benefits health care provides. About the REFLECT Trial (Study 304) REFLECT is an international, multicentre, open-label, randomised, non-inferiority Phase III study to compare the efficacy and safety of lenvatinib versus sorafenib as a first- line systemic treatment in patients with uHCC. Patients (n=954) at 183 trial sites in 21 countries were randomised to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival. The secondary efficacy endpoints of this study were progression-free survival, time to progression and objective response rate. The median OS for patients treated with lenvatinib was 13.6 months (95% CI: 12.1 – 14.9 months) compared to 12.3 months (95% CI: 10.4 – 13.9 months) for sorafenib (HR: 0.92; 95% CI: 0.79 – 1.06). Median PFS was 7.4 months (95% CI: 6.9–8.8 months) with lenvatinib with a median TTP of 8.9 months (95% CI; 7.4–9.2 months) compared to median PFS of 3.7 months (95% CI: 3.6–4.6 months) (HR: 0.66; 95% CI: 0.57 – 0.77; p<0.00001) and median TTP of 3.7 months on sorafenib (95% CI; 3.6–5.4 months) (HR 0.63; 95% CI; 0.53 – 0.73; p<0.00001). In addition, lenvatinib demonstrated significantly higher ORR (24%) compared to sorafenib (9%) (odds ratio: 3.13; 95% CI: 2.15-4.56; p<0.00001). ORR was evaluated using mRECIST. The most common treatment- emergent adverse events (TEAEs) of any grade among patients who received lenvatinib were hypertension (42.2%), diarrhoea (38.7%), decreased appetite (34.0%), and decreased weight (30.9%).ii In the sorafenib arm, the most common TEAEs were palmar-plantar erythrodysesthaesia (hand-foot syndrome) (52.4%), diarrhoea (46.3%), hypertension (30.3%), and decreased appetite (26.3%).ii TEAEs occurred in 98.7% of patients in the lenvatinib arm and 99.4% in the sorafenib arm of the study. About Hepatocellular Carcinoma (HCC ) Hepatocellular carcinoma (HCC) is a complex disease associated with a poor prognosis and accounts for approximately 90% of liver cancer cases worldwide. The incidence of liver cancer in Europe has been rising steadily over the past decade. uHCC is an advanced hard-to-treat stage of liver cancer that affects >70% of patients. HCC is the second most common cause of death from cancer worldwide, estimated to be responsible for nearly 746,000 deaths across the globe in 2012. In Europe, an estimated 71,000 people were diagnosed with liver cancer and 69,000 people died from this disease in 2012.