gms | German Medical Science

Introduction & Objectives: Recently, we have demonstrated in a randomized phase-III trial that an adjuvant vaccination with Reniale® reduces the risk of tumor progression in patients with non-metastatic renal cell carcinoma (RCC) [Lancet, 363(9409): 594-599, 2004]. We herein present the results of a secondary analysis of this trial performed in 2005 in response to questions raised by the European Agency for the Evaluation of Medicinal Products (EMEA).

Material & Methods: Between January 1997 and August 1998, 558 patients with a renal mass scheduled for radical nephrectomy were enrolled at 55 hospitals in Germany. Prior to radical nephrectomy all patients were centrally randomized to receive an adjuvant vaccination at 4-week intervals (Reniale® group) or no adjuvant therapy (control group). Primary end point of the trial was the reduction of the risk of tumor progression. Secondary major end points were overall survival (OS) and quality of life. OS data were collected for the time period of January 1997 to July 2005. The trial was performed according to ICH-GCP guidelines.

Results: This secondary ITT analysis was performed on 477 patients (233 patients in the Reniale group and 244 patients in the control group). Progression-free survival (PFS) remained in favor of the Reniale group (p = 0.0476, log-rank test). OS was not statistically significant different between both groups (p = 0.1185, log-rank test). Also, a secondary analysis of the per-protocol (PP) population was performed. There were 134 patients in the Reniale® group and 218 patients in the control group. Both end points (PFS and OS) were statistically significant in favor of the Reniale group (p = 0.024, log-rank test, for PFS and p = 0.0356, log-rank test, for OS, respectively). There was no serious vaccine-related adverse event. In general the vaccine was tolerated well.

Conclusions: The primary end point, i.e. reduction of the risk of tumor progression, remained reached in this secondary ITT analysis. Additionally, PFS and OS were prolonged in the Reniale® group compared to the control group (PP analysis). This is the first published randomized phase-III trial demonstrating a benefit from an adjuvant therapy in patients with non-metastatic RCC after radical nephrectomy.