The FINANCIAL — New data show that Afinitor (everolimus) Tablets significantly shrunk tumors in 33% of patients with relapsed non-Hodgkin's lymphoma (NHL) and Hodgkin's disease[1]. 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[2]. Up to 60% of patients with aggressive types of NHL, including DLBCL, may be cured with appropriate therapy[3]. However, NHL patients have a high risk of relapse after initial therapy and no treatments are currently available to reduce this risk[4],[5].
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% of patients with relapsed NHL and Hodgkin's disease treated with everolimus experienced a 50% or greater reduction in tumor size. This 33% overall response rate (ORR) is defined as complete or partial tumor shrinkage (95% confidence interval: 26-41%). The median time to disease progression for all 145 patients was 4.3 months (95% CI; 3.6-5.9 months) and the median duration of response for the 48 responders was 6.8 months (95% CI; 5.4-11.0 months). Nineteen responders remained progression free at 6 months[1].
"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 antitumor 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% of patients who will relapse after achieving a complete response on initial treatment, demonstrating an important unmet need[6].
EHA study details
The proof-of-concept, open-label, single-arm, multicenter Phase II study was designed to assess the efficacy and safety of everolimus in patients with relapsed/refractory aggressive or indolent NHL or Hodgkin's disease whose disease progressed despite prior treatment. Patients had received a median of four prior therapies (between one and 15 therapies). The study included patients with T-cell non-Hodgkin's lymphoma, Hodgkin's disease, follicular lymphoma, mantle cell lymphoma, DLBCL and small lymphocytic lymphoma; all of whom had experienced disease progression despite prior treatment. The primary endpoint of the study is to assess ORR. Secondary endpoints include assessment of progression-free survival (PFS), overall survival, time to disease progression and the safety profile of Afinitor[1].
In the trial, everolimus showed anticancer activity across multiple types of lymphoma, including T-cell non-Hodgkin's lymphoma (63% ORR), Hodgkin's disease (53% ORR), follicular lymphoma (50% ORR), mantle cell lymphoma (32% ORR), DLBCL (30% ORR) and small lymphocytic lymphoma (18% ORR)[1].
Patients received everolimus 10 mg daily and were evaluated monthly. Dose reductions to 5 mg daily and 5 mg every other day were permitted. Response was assessed after two cycles of treatment and periodically thereafter. Patients received a median of three cycles[1]. Overall, everolimus was well tolerated. The most commonly reported adverse events (grade 3 or 4; >10% patients) in this heavily pretreated population included anemia, neutropenia and thrombocytopenia[1].
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