– Lenvatinib is the first systemic therapy to demonstrate non-inferiority to sorafenib in the primary efficacy endpoint of overall survival
– Clinically meaningful and statistically significant improvements for lenvatinib were achieved in all secondary efficacy endpoints — progression-free survival, time to progression and objective response rate
WOODCLIFF LAKE, NJ, USA I June 4, 2017 I Eisai Inc. today announced results from the REFLECT study (Study 304), a Phase 3 trial evaluating lenvatinib (marketed as Lenvima®), the company’s multiple receptor tyrosine kinase inhibitor (including fibroblast growth factor receptors [FGFR] 1 – 4), for the first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). In the trial, lenvatinib demonstrated non-inferiority in overall survival (OS), the primary endpoint of the study, and also demonstrated statistically significant and clinically meaningful improvements on the secondary endpoints of progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR) when compared to sorafenib. These data will be presented in an oral presentation on June 4 at 8:12 a.m. CDT (Abstract No. 4001) at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago and will be published in a peer-reviewed journal. Lenvima is not approved for uHCC.
“Unresectable HCC is an extremely difficult-to-treat disease and we have seen no advancements in recent years for first-line systemic treatment, with sorafenib being the only FDA approved systemic therapy in this setting,” said Richard Finn, MD, Associate Professor of Medicine at the Geffen School of Medicine at UCLA and a member of UCLA’s Jonsson Comprehensive Cancer Center, and investigator of the study. “Based on the activity of lenvatinib demonstrated across all efficacy endpoints in the REFLECT study, I was very pleased to have been involved in this trial and look forward to continuing research to help patients with advanced liver cancer.”
“As patients with unresectable HCC are often symptomatic and face a poor prognosis, improving the rate of patients who respond to treatment is an important step forward for the liver cancer community,” said Ari Baron, MD, Chief of the Division of Hematology Oncology at California Pacific Medical Center and investigator of the study. “Based on the ORR demonstrated in this trial and the overall efficacy seen in patients treated with lenvatinib as compared to sorafenib, I’m delighted to see this move forward.”
The median OS for patients treated with lenvatinib was 13.6 months compared to 12.3 months for sorafenib (HR: 0.92; 95% CI: 0.79 – 1.06). Median PFS was 7.4 months with lenvatinib with a median TTP of 8.9 months compared to median PFS of 3.7 months (HR: 0.66; 95% CI: 0.57 – 0.77; p<0.00001) and median TTP of 3.7 months on sorafenib (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). Endpoints were evaluated using mRECIST and determined by investigator assessment. Independent review is currently underway.
In this study, the most common treatment-emergent adverse events (TEAEs) observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, decreased weight, and fatigue. Nine percent of patients treated with lenvatinib and 7% of patients treated with sorafenib discontinued treatment due to treatment-related adverse events. Forty-three percent of patients treated with lenvatinib and 30% of patients who received sorafenib experienced serious TEAEs.
“As a company that works tirelessly to serve patients with 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 are in need of additional treatment options,” said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai. “Based on these data, Eisai plans to submit regulatory applications for lenvatinib for the potential first-line treatment of patients with unresectable HCC and we look forward to working closely with the FDA and other regulatory bodies worldwide.”
This release discusses investigational uses for an FDA-approved product. It is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such FDA-approved product will gain FDA approval.
About the REFLECT Trial (Study 304)
REFLECT was an international, multicenter, randomized, open-label, non-inferiority Phase 3 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 randomized 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.
About Unresectable Hepatocellular Carcinoma (uHCC)
Hepatocellular carcinoma is the most common type of liver cancer, accounting for about 90% of cases of primary liver cancer in the United States. In 2015, liver cancer accounted for approximately 788,000 deaths globally, making it the second leading cause of cancer-related deaths worldwide. The prevalence and mortality rate of liver cancer has been rising steadily over the past decade. This year in the United States, more than 40,710 cases will be diagnosed and 28,920 people will die from their disease. uHCC, which could be Stage 3 or 4 disease, is an advanced stage of liver cancer that cannot be removed by surgery. Approximately 45% of patients have Stage 3 or 4 HCC at diagnosis and there are limited treatment options available for patients with advanced disease.
About LENVIMA® (lenvatinib)
LENVIMA® (lenvatinib) is a kinase inhibitor that is indicated for:
- Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
- Renal Cell Cancer (RCC): in combination with everolimus for patients with advanced RCC following one prior anti-angiogenic therapy.
Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thought to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
SOURCE: Eisai
Post Views: 99
– Lenvatinib is the first systemic therapy to demonstrate non-inferiority to sorafenib in the primary efficacy endpoint of overall survival
– Clinically meaningful and statistically significant improvements for lenvatinib were achieved in all secondary efficacy endpoints — progression-free survival, time to progression and objective response rate
WOODCLIFF LAKE, NJ, USA I June 4, 2017 I Eisai Inc. today announced results from the REFLECT study (Study 304), a Phase 3 trial evaluating lenvatinib (marketed as Lenvima®), the company’s multiple receptor tyrosine kinase inhibitor (including fibroblast growth factor receptors [FGFR] 1 – 4), for the first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). In the trial, lenvatinib demonstrated non-inferiority in overall survival (OS), the primary endpoint of the study, and also demonstrated statistically significant and clinically meaningful improvements on the secondary endpoints of progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR) when compared to sorafenib. These data will be presented in an oral presentation on June 4 at 8:12 a.m. CDT (Abstract No. 4001) at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago and will be published in a peer-reviewed journal. Lenvima is not approved for uHCC.
“Unresectable HCC is an extremely difficult-to-treat disease and we have seen no advancements in recent years for first-line systemic treatment, with sorafenib being the only FDA approved systemic therapy in this setting,” said Richard Finn, MD, Associate Professor of Medicine at the Geffen School of Medicine at UCLA and a member of UCLA’s Jonsson Comprehensive Cancer Center, and investigator of the study. “Based on the activity of lenvatinib demonstrated across all efficacy endpoints in the REFLECT study, I was very pleased to have been involved in this trial and look forward to continuing research to help patients with advanced liver cancer.”
“As patients with unresectable HCC are often symptomatic and face a poor prognosis, improving the rate of patients who respond to treatment is an important step forward for the liver cancer community,” said Ari Baron, MD, Chief of the Division of Hematology Oncology at California Pacific Medical Center and investigator of the study. “Based on the ORR demonstrated in this trial and the overall efficacy seen in patients treated with lenvatinib as compared to sorafenib, I’m delighted to see this move forward.”
The median OS for patients treated with lenvatinib was 13.6 months compared to 12.3 months for sorafenib (HR: 0.92; 95% CI: 0.79 – 1.06). Median PFS was 7.4 months with lenvatinib with a median TTP of 8.9 months compared to median PFS of 3.7 months (HR: 0.66; 95% CI: 0.57 – 0.77; p<0.00001) and median TTP of 3.7 months on sorafenib (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). Endpoints were evaluated using mRECIST and determined by investigator assessment. Independent review is currently underway.
In this study, the most common treatment-emergent adverse events (TEAEs) observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, decreased weight, and fatigue. Nine percent of patients treated with lenvatinib and 7% of patients treated with sorafenib discontinued treatment due to treatment-related adverse events. Forty-three percent of patients treated with lenvatinib and 30% of patients who received sorafenib experienced serious TEAEs.
“As a company that works tirelessly to serve patients with 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 are in need of additional treatment options,” said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai. “Based on these data, Eisai plans to submit regulatory applications for lenvatinib for the potential first-line treatment of patients with unresectable HCC and we look forward to working closely with the FDA and other regulatory bodies worldwide.”
This release discusses investigational uses for an FDA-approved product. It is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such FDA-approved product will gain FDA approval.
About the REFLECT Trial (Study 304)
REFLECT was an international, multicenter, randomized, open-label, non-inferiority Phase 3 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 randomized 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.
About Unresectable Hepatocellular Carcinoma (uHCC)
Hepatocellular carcinoma is the most common type of liver cancer, accounting for about 90% of cases of primary liver cancer in the United States. In 2015, liver cancer accounted for approximately 788,000 deaths globally, making it the second leading cause of cancer-related deaths worldwide. The prevalence and mortality rate of liver cancer has been rising steadily over the past decade. This year in the United States, more than 40,710 cases will be diagnosed and 28,920 people will die from their disease. uHCC, which could be Stage 3 or 4 disease, is an advanced stage of liver cancer that cannot be removed by surgery. Approximately 45% of patients have Stage 3 or 4 HCC at diagnosis and there are limited treatment options available for patients with advanced disease.
About LENVIMA® (lenvatinib)
LENVIMA® (lenvatinib) is a kinase inhibitor that is indicated for:
- Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
- Renal Cell Cancer (RCC): in combination with everolimus for patients with advanced RCC following one prior anti-angiogenic therapy.
Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thought to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
SOURCE: Eisai
Post Views: 99
