Harnessing the Immune System in Pancreatic Cancer

摘要: Managing patients with metastatic pancreatic adenocarcinoma (mPDA) is a challenging proposition for any treating oncologist. Although the potency of first-line therapies has improved approvals FOLFIRINOX and gemcitabine plus nab-paclitaxel, many are unable to derive significant benefit from later lines therapy upon progression. Enrollment on clinical trials remains among best options mPDA in all therapy. At our institution, we routinely check microsatellite instability (MSI-H) perform next-generation sequencing (NGS) at time diagnosis good performance status patients. MSI-H only found 1% mPDA, given pembrolizumab’s tissue-agnostic approval tumors later-line settings, it viable option when deciding subsequent Any use immune investigational outside setting. NGS can identify BRCA or other DNA damage response (DDR) defects which predict sensitivity platinum-based influence choice both initial It also rare actionable genomic alterations such as HER2 (2%) TRK fusions (0.1%) offer enrollment agents targeting these identified alterations. We believe enrolling immune-modulating critical determine if there patient subsets, setting, who would approaches. Immunotherapy’s general tolerability potential generate durable responses make particularly appealing single-modality immunotherapy checkpoint inhibitors vaccines have not demonstrated efficacy this disease, combinatorial strategies unique aspects PDA including tumor microenvironment desmoplastic stroma shown preclinical early-phase success. Validating treatments later-phase prospective studies essential making routine component treatment armamentarium