The European Commission (EC) has approved Afinitor® (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. Nearly 40% of all RCC patients have advanced cancer at time of diagnosis, meaning that their tumors have spread outside of the kidneys[1]. Standard initial treatment for these patients may include VEGF-targeted therapies[2]. Prior to Afinitor, there were no proven treatment options for advanced RCC patients whose cancer progressed while on or after treatment with VEGF-targeted therapy.
"This approval means that across Europe thousands of patients with advanced kidney cancer now have the opportunity for a clear treatment path with Afinitor if their disease progresses after treatment with a targeted therapy," said David Epstein, President and CEO, Novartis Oncology, Novartis Molecular Diagnostics.
The EC based its approval of Afinitor on data from a pivotal Phase III trial demonstrating that Afinitor, when compared with placebo, more than doubled the median time without tumor growth or death in patients with advanced kidney cancer whose disease progressed following prior VEGF-targeted therapy (4.9 vs. 1.9 months). Additionally, the data showed Afinitor reduced the risk of disease progression or death by 67% based on the primary endpoint of progression-free survival (PFS) (hazard ratio=0.33 with 95% confidence interval 0.25 to 0.43; P<0.0001)[3].
Several European treatment guidelines have been updated to recommend Afinitor as a second-line advanced kidney cancer therapy after progression on targeted therapies, including those from the European Association of Urology (EAU), the Spanish Oncology Genitourinary Group (SOGUG), the European Organisation for Research and Treatment of Cancer (EORTC), the European Society for Medical Oncology (ESMO) and the UK Consensus Guidelines[4],[5],[6],[7],[8].
The EC decision applies in all 27 European Union (EU) member states. Afinitor is currently under regulatory review in Switzerland, Japan and other countries.
Study detailsThe approval is based on data from RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily), the largest Phase III clinical trial to study the effects of an oral mTOR inhibitor in advanced RCC patients whose cancer progressed despite prior VEGF-targeted treatment[9]. In February 2008, based on a recommendation from an independent data monitoring committee, Novartis stopped the trial after interim results showed that patients receiving Afinitor experienced a significant delay in cancer progression or death compared with patients receiving placebo. This international, multicenter, randomized, double-blind clinical trial involved 416 patients with advanced RCC whose cancer progressed despite prior treatment with sunitinib or sorafenib. Prior therapy with bevacizumab, interferon alfa and interleukin-2 was allowed. Patients were randomized to receive Afinitor (10 mg) daily or placebo, in conjunction with best supportive care. The primary endpoint of the study was PFS, which was assessed via a blinded, independent, central radiological review[9]. About RCC
Renal cell carcinoma, which accounts for approximately 2% of all new cancers, is often referred to as kidney cancer[10]. The occurrence rates of RCC are rising steadily around the world due, in part, to smoking and obesity[11]. In the EU, there were more than 63,000 new cases of RCC diagnosed and more than 26,000 people died from the disease in 2006[12]. In RCC, cancer cells develop in the lining of the kidney's tubes and grow into a tumor. If left untreated, the tumor can spread to neighboring lymph nodes and eventually to other organs[13],[14]. About Afinitor
In the EU, Afinitor is indicated for patients with advanced RCC whose disease progressed on or after treatment with VEGF-targeted therapy. Afinitor is also approved in the US to treat advanced RCC after failure of treatment with sunitinib or sorafenib. In cancer cells, Afinitor continuously targets mTOR, a protein that acts as a central regulator of tumor cell division, blood vessel growth and cell metabolism. Afinitor is being studied in multiple cancer types, including RCC, neuroendocrine, breast, gastric and hepatocellular carcinoma (HCC), as well as tuberous sclerosis complex (TSC) and non-Hodgkin's lymphoma. The active ingredient in Afinitor is everolimus, which is available in different dosage strengths under the trade name Certican® for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003. For more information on Afinitor, visit www.afinitor.com. About Novartis
Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2008, the Group's continuing operations achieved net sales of USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 99,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com. 1.The University of Texas MD Anderson Cancer Center. Kidney Cancer. Available at http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/kidney-cancer/index.html. Accessed June 2009.
2. National Comprehensive Cancer Network. "NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer." Available at http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf. Accessed March 2009.
3. Afinitor® (everolimus) tablets prescribing information. Basel, Switzerland: Novartis International AG; August 2009. 4. Ljungberg, B. et al. Guidelines on Renal Cell Carcinoma. European Association of Eurology. March 2009. Available at http://www.uroweb.org/fileadmin/tx_eauguidelines/2009/Full/RCC.pdf. Accessed June 2009.
5. Bellmunt, J. et al. Recommendations from the Spanish Genitourinary Group for the treatment of metastatic renal cell cancer. Cancer Chemotherapy and Pharmacology. March 2009;63 Suppl 1:S1-13.
6. Reijke, T. et al. EORTC-GU expert opinion on metastatic renal cell cancer. European Journal of Cancer. March 2009;45(5):765-73.
7. Escudier, B. et al. Renal cell carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Annals of Oncology 20: Suppl 4:iv81-ivb2, 2009.
8. Nathan, P. et al. UK guidelines for the systemic treatment of renal cell carcinoma. British Journal of Hospital Medicine. Vol. 70, Iss. 5, May 13, 2009.
9. Escudier, B. et al. Phase-3 randomized trial of everolimus (RAD001) vs. placebo in metastatic renal cell carcinoma. Presented at the European Society for Medical Oncology (ESMO) 33rd Congress on September 16, 2008.
10. McLaughlin JK, et al. Epidemiologic aspects of renal cell carcinoma.Semin Oncol. 2006;33(5):527-533.
11. Eisen, et. al. Sorafenib for Older Patients with Renal Cell Carcinoma. Journal of the Natational Cancer Institute. 2008;100(20):1454-1463.
12. Ferlay, J. et al. Estimates of the cancer incidence and mortality in Europe in 2006. Annals of Oncology.18(3):581-92. March 2007.
13. National Cancer Institute. "General Information About Renal Cell Cancer." Available at http://www.cancer.gov/cancertopics/pdq/treatment/renalcell/patient. Accessed March 2009.
14. American Cancer Society. "How Is Kidney Cancer (Renal Cell Carcinoma) Staged?" Available at http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_kidney_cancer_staged_22.asp?rnav=cri. Accessed March 2009.