RE:RE:RE:RE:RE:RE:ONCY pelareorep demonstrates 69% ORR in pancreatic cancerBackground .... mPDAC is a biologically aggressive cancer that is often characterized by clinically evident disease progression during first-line treatment (pain, fatigue, anorexia, weight loss, constipation, fever, diabetic decompensation, etc.) with a deterioration of the patient performance status (PS) that limits subsequent treatments. Several complications can also arise, such as duodenal stenosis, obstruction of biliary stents and cholangitis, gastrointestinal bleeding and intestinal obstructions, which further limit the possibility of accessing second-line chemotherapy. In this context, it is not surprising that few data from large randomized trials are available. To date, there are no clear data on the superiority of a specific chemotherapy regimen due to the lack of adequate comparisons.
In advanced PDAC, the choice of which chemotherapy to use in the second-line setting basically depends on the treatments used in the first-line setting, residual toxicities (e.g., peripheral neuropathy), patient PS, age and comorbidities. The ability of patients in different countries to access a specific treatment should also be considered due to the limitations of regulatory agencies.
PDAC are characterized by the presence of an abundant desmoplastic stroma composed of fibroblasts, extracellular matrix, immune cells and stellate cells. Immune cells infiltrating this stroma are mostly represented by tumour-associated macrophages, myeloid-derived suppressor cells and Treg cells, with very few effector T cells. Numerous trials are underway aimed at converting the pancreatic tumour microenvironment from immunosuppressive to immunosensitive[68,69]; however, to date, there is no indication for second-line immunotherapy treatments in chemorefractory disease. A PD-1 (programmed cell death protein 1) ICI, Pembrolizumab, has been approved by the FDA for diseases with microsatellite instability, regardless of tumour site[70]. However, this indication has not yet been approved by EMA, and in Europe, it is therefore not possible to prescribe immunotherapy in this setting outside of clinical trials.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108033/