Pancreatic cancer, treatment options, and GI-4000

Abstract

Although pancreatic cancer is but the eleventh most prevalent cancer in the US, it is predicted that of all the patients newly diagnosed with this disease in 2014, only 27% will still be alive at the end of the first year and only 6% will make it past 5 years. The choice of chemotherapy in the treatment of pancreatic cancer is dependent on disease stage and patient performance status but, in general, the most widely used approved regimens include 5-fluorouracil (5-FU) combinations and gemcitabine combinations. Recent therapeutic strategies have resulted in an improvement in survival of patients with pancreatic cancer but the magnitude of change is disappointing and vast improvements are still needed. The goal of immunotherapy is to enhance and guide the body's immune system to recognize tumor-specific antigens and mount an attack against the disease. Among newer immune therapies, GI-4000 consists of 4 different targeted molecular immunogens, each containing a different Ras protein (antigen) encoded by the most commonly found mutant RAS genes in solid tumors--RAS mutations exist in over 90% of pancreatic ductal adenocarcinomas. We will review pancreatic cancer epidemiology and its current treatment options, and consider the prospects of immunotherapy, focusing on GI-4000. We discuss the potential mechanism of action of GI-4000, and the performance of this vaccination series thus far in early phase clinical trials.

Figure 1.

GI-4000 Series: Four different strains: GI-4014, -4015, -4016, -4020 of heat-inactivated S. Cerevisiae; each express a mutated Ras fusion protein. The mutations of RAS represent the most common mutations found in solid tumors via genotype analysis. Each strain bares a fusion protein that is inclusive of 3 different RAS mutation combinations; 2 of the mutations are found on codon 61 and the other on codon 12. (http://meetinglibrary.asco.org/content/40075?format = posterImg) – Permission required

Figure 2.

Overall Survival (OS) of patients with a G12R mutation compared with all other Ras mutations, regardless of treatment.