HATFIELD, England, June 4, 2017 /PRNewswire/ --
- Lenvatinib is the first systemic therapy to demonstrate non-inferiority to the current standard of care in the primary efficacy endpoint of overall survival and show statistically significant improvements across secondary efficacy endpoints including median time to progression and progression-free survival.
- Pivotal Phase III results presented as an oral presentation at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) Chicago, 2-6 June 2017 and will inform basis of regulatory filings worldwide.
Today Eisai announces clinically meaningful data from a pivotal Phase III study which show that lenvatinib is non-inferior to sorafenib in median overall survival (OS) for the first-line systemic treatment of patients with unresectable hepatocellular carcinoma (uHCC). These data will be presented today in an oral presentation (Abstract no. 4001) at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) Chicago, 2-6 June 2017.
The REFLECT study (Study 304) is the first non-inferiority trial to show statistically significant results for a systemic therapy versus the current standard of care in uHCC, also demonstrating improvements in the secondary endpoints of progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR).
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.
"Results from this large Phase III trial demonstrate the potential of lenvatinib to improve the outcomes of liver cancer patients, and provide an overall survival benefit that is non-inferior to sorafenib, currently the only systemic therapy approved by the European Medicines Agency for unresectable HCC," commented Professor Jeff Evans, Professor of Translational Cancer Research, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow and investigator of the study. "For a decade there has been no advance in the first-line systemic treatment of uHCC in Europe, so this data supports a potential new option for liver cancer patients that offers greater choice."
REFLECT is a Phase III open label non-inferiority study to compare the efficacy and safety of lenvatinib (n=478) versus sorafenib (n=476) as a first-line systemic treatment in patients with uHCC. 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%). 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%). TEAEs occurred in 98.7% of patients in the lenvatinib arm and 99.4% in the sorafenib arm of the study.
"Lenvatinib is already indicated for the treatment of radioiodine refractory differentiated thyroid cancer and advanced renal cell carcinoma, and continues to show compelling results in difficult-to-treat cancers. Eisai is excited by the potential of the results seen with lenvatinib in Study 304 to provide improved outcomes for patients with unresectable HCC, who face a poor prognosis and are in need of additional treatment options," said Gary Hendler, Chairman & CEO EMEA, Chief Commercial Officer, Oncology Business Group at Eisai. "Based on these data, Eisai plans to submit regulatory applications for lenvatinib for the first-line treatment of patients with unresectable HCC and we look forward to working closely with the European Medicines Agency and other regulatory bodies worldwide."
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.
Notes to Editors
About the REFLECT Trial (Study 304) 
REFLECT is an international, multicentre, randomised, open-label, 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.
Lenvatinib, discovered and developed by Eisai, is an oral multikinase inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor-alpha, and RET and KIT proto-oncogenes., Lenvima® (lenvatinib) is approved in the EU and the US for specific patient populations:
In the European Union lenvatinib is indicated:
- Under the brand name Lenvima® 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).
- Under the brand name Kisplyx® in combination with everolimus in the European Union for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor (VEGF)-targeted therapy.
About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including Oncology and Neurology.
As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.
For more information about Eisai Co., Ltd., please visit www.eisai.com.
1. Cheng A, et al. Phase 3 trial of lenvatinib vs sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). American Society for Clinical Oncology annual meeting 2017; Abstract No. 4001
2. Weledj E, et al. How grim is hepatocellular carcinoma? Annals of Medicine & Surgery 2014; 3(3):71-76
3. McGlynn KA, et al. The Global Epidemiology of Hepatocellular Carcinoma, Present and Future. Clin Liver Dis 2011; 15(2):223-243
4. Lencioni R, et al. Treatment of Intermediate/Advanced Hepatocellular Carcinoma in the Clinic: How Can Outcomes Be Improved? The Oncologist 2010;15:42-52
5. World Health Organization. Estimated Incidence, Mortality and Prevalence Worldwide in 2012. GLOBOCAN Cancer Fact Sheets: Liver Cancer. Available at: http://gco.iarc.fr/today/data/pdf/fact-sheets/cancers/cancer-fact-sheets-7.pdf Accessed May 2017.
6. Matsui J, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer 2008;122:664-671.
7. Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Medicinal Chemistry Letter 2010.