Clinical prognostic factors associated with outcome in renal cell cancer (RCC) patients treated with modified vaccinia ankara plus tumor-associated antigen 5T4 (MVA-5T4).

Abstract

e15545 Background: Development of MVA-5T4 as an immunotherapeutic vaccine led to studies demonstrating it is safe and highly immunogenic as a monotherapy or combination (Amato 2008 Clin Cancer Res, Amato 2008 J Immunother, Amato 2009 J Immunother). Antitumor activity has been minimal. We examined identifiable clinical factors to develop a prognostic model to select patients for vaccine immunotherapy. Methods: Clinical data from 3 phase II studies were received for a total of 50 patients treated with MVA-5T4 alone, MVA-5T4 plus interferon-α or MVA-5T4 plus interleukin-2. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analyses were constructed using COX Proportional Hazard model and step-wise procedure. The model was validated by measuring the overall concordance index. Results: For the entire population, median PFS was 3.6 months (range 0.9-42.8 months), and median OS was 12.4 months (range 1.0-45.6 months). Univariate analysis revealed 10 clinical factors associated with PFS and 9 clinical factors associated with OS. Multivariate analysis identified 5 factors associated with PFS benefit (ECOG status ≥1, lymphocytes <25, >2 metastatic sites, neutrophils ≥69, albumin <4) and 6 factors associated with OS benefit (ECOG status ≥1, >2 metastatic sites, neutrophils ≥69, platelets >300, prior treatment with tyrosine kinase inhibitors/immunotherapy, Furham grade of 3/4). The prognostic model was divided into 3 categories. Patients with 0-1 factors (favorable) had a median PFS of 9.4 months and OS of 26.2 months, patients with 2-3 factors (intermediate) had a median PFS of 3.0 months and OS of 9.1 months, and patients with 4+ factors (poor) had a median PFS of 2.0 months and OS of 2.0 months. Conclusions: This analysis identified 7 available clinical factors that can classify patients with mRCC into 3 risk groups with various outcomes. Further validation of this model will identify which patients most likely to respond to MVA-5T4 as well as other vaccines. This will allow for the appropriate application of treatment to patients most likely to benefit.