Kidney cancer is among the ten most frequently occurring cancers in Western (countries) communities.[13] About 270,000 cases of kidney cancer are diagnosed globally each year and 116,000 people die from the disease.[13]Approximately 90% of all kidney cancers are renal cell carcinomas (RCC).[13]
About Lenvatinib
Lenvatinib 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.[14],[15]
Lenvatinib is indicated in the European Union 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).[16] Lenvatinib is approved for the treatment of refractory thyroid cancer in the United States, Switzerland, the European Union, Canada, Russia, Australia, South Korea, Israel, Singapore, Japan and Brazil.
In September 2016, the European Commission issued Marketing Authorisation for lenvatinib in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF)-targeted therapy.
About SELECT[4]
SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) is a multicentre, randomised, double-blind, placebo-controlled phase III study of patients with radioiodine-refractory differentiated thyroid cancer, treated with once-daily, oral lenvatinib (24mg). The study enrolled 392 patients in over 100 sites in Europe, Americas, Asia, and Australia.
About Study 205[17]
Study 205 is a pivotal randomised phase II study that evaluated 153 people living with unresectable advanced renal cell carcinoma who had progressed after one previous VEGF therapy.[17] Patients experienced a median progression-free survival of 14.6 months when treated with lenvatinib in combination with everolimus (n=51), compared with 5.5 months for those who received everolimus alone (n=50) (HR 0.40; 95% CI: 0.24-0.67; p=0.0005).[17] Updated median overall survival in the study population was 25.5 months in the lenvatinib plus everolimus group compared with 15.4 months in the everolimus group (HR 0.59; 95% CI 0.36 - 0.97).[17]
For lenvatinib in combination with everolimus, the most common any-grade treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhoea, decreased appetite and fatigue.[17] The most common TEAEs of Grade 3 or higher were diarrhoea, fatigue and hypertension.[17]
About Metastatic Breast Cancer
More than 300,000 women are diagnosed with breast cancer in Europe every year and about one third subsequently develop metastatic disease.[18] At this advanced stage, the cancer spreads beyond the breast to other parts of the body.
About Soft Tissue Sarcomas
Soft tissue sarcomas is a collective term for a diverse group of malignant tumours. Unlike other cancers, soft tissue sarcomas are often diagnosed with localised disease, and many are amenable to complete surgical removal, yet relapse rates can be as high as 50%. [19] Only 50% of people with soft tissue sarcomas are expected to live up to five years. [20] Outcomes for patients with advanced disease are poor, with median survival around one year or less.[21]
Leiomyosarcomas are one of the more common types of sarcoma to develop in adults. They develop from smooth muscle cells and can start anywhere in the body.[22] Liposarcomas arise from fat cells and can occur anywhere in the body. Leiomyosarcomas and liposarcomas make up approximately 30% of all cases of soft tissue sarcomas.[21]
About Halaven(R)(eribulin)
Eribulin is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics that prevents cell division.
Eribulin is indicated in the European Union for the treatment of adults with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless patients were not suitable for these treatments.[23]
The European Commission approved in May 2016 a variation to the terms of the Marketing Authorisation of eribulin for the treatment of adult patients with unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease.
Global Phase III Clinical Study 309[24]
Study 309 is a randomised, open-label, multicentre phase III study comparing the efficacy and safety of eribulin mesilate (1.4 mg/m[2], IV on days 1 and 8) to dacarbazine (850-1200 mg/m[2], IV on day 1) in a 21-day cycle. A total of 452 patients (aged 18 or over) with soft tissue sarcomas were randomised. The primary endpoint of the study was overall survival. Additional endpoints included progression-free survival and quality of life.
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 multiple 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 http://www.eisai.com.
References
1. Velcheti V, et al. Phase 2 study of lenvatinib (LN) in patients (Pts) with RET fusion-positive adenocarcinoma of the lung. European Society for Medical Oncology 2016; Poster: 1204PD
2. Taylor M, et al. A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEM) in patients with selected solid tumours. European Society for Medical Oncology 2016; Poster: 776PD
3. Robinson B, et al. Responses in specific metastases following treatment with lenvatinib (LN): results from the phase 3 SELECT trial. European Society for Medical Oncology 2016; Poster: 962P
4. Schlumberger M, et al. Lenvatinib versus placebo in radioiodine-refractory differentiated thyroid cancer. NEJM 2015; 372: 621-630. Available at http://www.nejm.org/doi/full/10.1056/NEJ... September 2016
5. Kimura T, et al. The antitumor activity of lenvatinib (LEN) in combination with everolimus (EVE) in human renal cell carcinoma (RCC) xenograft models is dependent on VEGFR and FGFR signalling. European Society for Medical Oncology 2016; Poster: 6P
6. Kato Y, et al. Lenvatinib mesilate (LEN) enhanced antitumor activity of a pd-1 blockade agent by potentiating th1 immune response, European Society for Medical Oncology (ESMO) meeting 2016, Poster: 2PD
7. De Paz L, et al. CASCADE study: Pronounced decline in treatment efficacy through the metastatic life of breast cancer patients. European Society for Medical Oncology (ESMO) meeting 2016, Poster: 248P
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