New data show that Afinitor (everolimus) tablets significantly shrunk tumours in 33 per cent of patients with relapsed non-Hodgkin's lymphoma (NHL) and Hodgkin's disease. Based on results from this study and other early-stage research, Novartis has initiated a phase III trial in the most common NHL, diffuse large B-cell lymphoma (DLBCL).
Non-Hodgkin's lymphoma and Hodgkin's disease, also known as Hodgkin's lymphoma, refer to a variety of cancers affecting the immune system, such as DLBCL, mantle cell lymphoma and follicular lymphoma. Up to 60 per cent of patients with aggressive types of NHL, including DLBCL, may be cured with appropriate therapy. However, NHL patients have a high risk of relapse after initial therapy and no treatments are currently available to reduce this risk.
The phase-II open-label trial of 145 lymphoma patients was presented at the 14th annual European Hematology Association congress in Berlin, Germany. Results show that 33 per cent of patients with relapsed NHL and Hodgkin's disease treated with everolimus experienced a 50 per cent or greater reduction in tumour size. This 33 per cent overall response rate (ORR) is defined as complete or partial tumour shrinkage (95 per cent confidence interval: 26-41 per cent). The median time to disease progression for all 145 patients was 4.3 months (95 per cent CI; 3.6-5.9 months) and the median duration of response for the 48 responders was 6.8 months (95 per cent CI; 5.4-11.0 months). Nineteen responders remained progression free at 6 months.
"We continue to see the potential of Afinitor in multiple types of cancer," said Alessandro Riva, MD, executive vice president, Global Head, Novartis Oncology Development. "These latest data show an antitumour effect in lymphoma that support the rationale for a Phase III study of Afinitor to prevent relapse in patients with diffuse large B-cell lymphoma, where there is a significant unmet medical need."
Novartis has initiated PILLAR-2 (PIvotaL Lymphoma triAls of RAD001), a phase III trial investigating adjuvant treatment with everolimus (RAD001) in poor-risk patients with DLBCL who achieved complete remission with first-line rituximab combined with chemotherapy. This worldwide study will evaluate the potential of everolimus to extend disease-free survival in patients with DLBCL. The longer a patient with DLBCL is in remission the higher their likelihood to remain disease-free. There is no approved therapy for the approximately 50 per cent of patients who will relapse after achieving a complete response on initial treatment, demonstrating an important unmet need.
Afinitor has been approved by the US Food and Drug Administration (FDA) as the first oral, daily therapy (5 mg and 10 mg tablets) to treat advanced kidney cancer after failure of treatment with sunitinib or sorafenib. Recently, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion supporting EU approval of Afinitor to treat patients with advanced renal cell carcinoma whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy.
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. Novartis has also filed regulatory submissions with other regulatory agencies globally for the treatment of advanced kidney cancer. Afinitor is being studied in multiple cancer types, including NET, breast, gastric and hepatocellular carcinoma (HCC), as well as tuberous sclerosis complex (TSC) and NHL.
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.