Tag: Pancreatic Cancer

SUMMARY: The authors in this study took a novel approach and tested a combination of two vaccines in patients with metastatic pancreatic adenocarcinoma. Traditional vaccination against specific bacterial and viral infections involves the injection of the specific weakened bacteria/virus or a structural component of the bacteria or virus. The body then mounts an immune response and is ready to respond to an infection associated with that specific bacteria or virus. Use of vaccines in cancer treatment is based on the same principle. The two vaccines studied were GVAX and CRS-207. GVAX is an allogeneic whole cell vaccine developed from pancreatic cancer cell lines. These cancer cells are irradiated, to prevent them from dividing and are genetically modified to secrete GM-CSF (Granulocyte Macrophage Colony Stimulating Factor). GM-CSF is important for the growth and activation of dendritic cells also known as Antigen Presenting Cells. This vaccine when injected attracts the dendritic cells to the vaccine injection site and the dendritic cells in turn, pick up the antigens from the vaccine and present them to the patient’s immune system. The immune system then mounts a response by activating tumor specific T-cells. This vaccine therefore theoretically boosts the body’s immune system to fight the patient’s tumor, without causing collateral damage. The second vaccine CRS-207 is live-attenuated (weakened) Listeria monocytogenes bacterium which expresses mesothelin and stimulates innate and adaptive immunity. It is genetically engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be expressed at higher levels on pancreatic cancer cells than on normal cells. Previous studies have demonstrated that survival can be improved by induction of mesothelin specific T-cell responses. In this study, 90 patients with metastatic pancreatic adenocarcinoma were randomly assigned in a 2:1 ratio to receive two doses of GVAX followed by four doses of CRS-207 or six doses of GVAX alone. Treatment was given every 3 weeks and low-dose CYTOXAN® (Cyclophosphamide) was given IV, the day before GVAX in both groups, to inhibit regulatory (suppressive) T-cells. More than 80% of the patients had at least one prior treatment for metastatic disease and 50% had two or more prior treatments. The primary endpoint was overall survival. Secondary endpoints included safety, clinical and immune responses. At a planned interim analysis, the median overall survival was 6.1 months with the combination of two vaccines vs 3.9 months with GVAX alone (HR=0.54, P=0.011), a 46% reduction in risk of death with the combination immunotherapy. The median overall survival in patients who received three total doses which included at least two doses of GVAX and at least one dose of CRS-207 was 9.7 months compared to 4.6 months for GVAX alone (HR=0.44, P=0.0074), a 56% reduction in the risk of death. In the subgroup of patients who had had two or more prior chemotherapy regimens, combination immunotherapy given as third line therapy or greater resulted in a median overall survival of 5.1 months vs 3.7 months with GVAX alone (HR=0.34, P=0.001), a 66% reduction in risk of death. Stabilization of tumor marker CA19-9 was seen in 32% of patients receiving combination immunotherapy vs 13% in those who received GVAX alone (P=0.06). The one year survival probability doubled with the dual vaccine with an estimated one year survival of 24% for the combination immunotherapy group and 12% for the GVAX alone group. Toxicities included local reactions after GVAX and transient fevers, chills, and lymphopenia after CRS-207 administration. The authors concluded that immunotherapy with a combination of two vaccines improved overall survival in patients with metastatic pancreatic carcinoma, who have failed prior therapies. Le DT, Wang-Gillam A, Picozzi V, et al. J Clin Oncol 32, 2014 (suppl 3; abstr 177)