1. In a phase II trial of 90 patients with metastatic pancreatic adenocarcinoma, the combination of two cancer vaccines, Cy/GVAX and CRS-207, was associated with increased overall survival compared to Cy/GVAX alone.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Previous studies have demonstrated the use of cancer vaccines in the treatment of metastatic pancreatic ductal adenocarcinoma (PDA). GVAX pancreas is a granulocyte-stimulating factor stimulating vaccine given with cyclophosphamide (Cy/GVAX) to induce T-cell activity against mesothelin, a PDA-associated tumor antigen. CRS-207 is a recombinant live-attenuated vaccine designed to increase mesothelin secretion in antigen-presenting cells, and may increase the effectiveness of Cy/GVAX via a heterologous prime/boost mechanism. A previous phase I trial demonstrated increased survival in patients treated with both Cy/GVAX and CRS-207 versus Cy/GVAX alone. The purpose of this study was to present the results of the phase II trial analyzing this synergistic effect. Ninety patients with metastatic PCA were assigned to either Cy/GVAX with CRS-207 or Cy/GVAX alone. The primary outcome was overall survival and safety of the combined immunotherapy. At the conclusion of the trial, patients treated with the combination immunotherapy was associated with a 56% (2.2 months) improvement in overall survival compared to Cy/GVAX alone. The majority of the adverse events associated with the combination immunotherapy were injection site reactions. The results of this trial support the use of combined Cy/GVAX and CRS-207 as a treatment modality of metastatic pancreatic cancer; however, given the small sample size, further randomized control trials are needed to confirm the safety and efficacies of these immunotherapies.
Click to read the study in JCO
In-Depth [randomized controlled trial]: This multicenter, randomized phase II trial included a total of 90 patients with metastatic pancreatic ductal adenocarcinoma (PDA). The patients must have had at least one prior therapy regimen and have a life expectancy of greater than 12 weeks. Patients were randomized at a ratio of 2:1 to the treatment arms, either 2 doses of Cy/GVAX followed by 4 doses of CRS-207, or 6 doses of Cy/GVAX alone. The primary endpoint was overall survival, and secondary endpoints were safety and clinical response to treatment. Mean follow-up was 3.4 months. The authors also assessed mesothelin-specific CD8+ T cells. Mean number of doses given in in the combination arm and Cy/GVAX alone was 5.5(±4.5) and 3.7(±2.2), respectively. At the conclusion of the trial, the overall survival was 6.1 months in the combined arm and 3.9 months with Cy/GVAX alone (HR=0.59; 95%CI: 0.36-0.97; p = 0.02). The most frequent adverse events with the combination arm were injection site reactions (erythema: 77%, induration: 71%, pain: 62%), nausea (53%), vomiting (43%), chills (67%), fever (62%) and fatigue (53%). There was no significant difference in mesothelin-specific CD8+ T cell levels between treatment arms.
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