Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive cancers, with minimal improvement in five-year survival rates over the past 45 years. The standard treatments for PDAC are limited to conventional chemotherapies, with multi-agent combinations such as gemcitabine plus nab-paclitaxel and FOLFIRINOX being the first-line choices. These treatments offer a median overall survival benefit of around 2–4 months over gemcitabine monotherapy in advanced disease. Despite significant funding from the National Cancer Institute (NCI) and other organizations, there have been no significant breakthroughs in PDAC treatment comparable to those seen in other cancers.
Clinical trials represent the forefront of new therapy development, with 430 registered interventional trials focused on PDAC as of May 18, 2019. These trials span various phases, with the majority enrolling patients with metastatic pancreatic cancer. The therapeutic interventions under investigation include novel drugs, monoclonal antibodies, gene therapies, and cell therapies, targeting a wide range of biologic mechanisms such as the immune system, DNA and cell cycle, cell signaling, and metabolism.
Among the phase III trials, only 14 are testing novel interventions in the PDAC space, with some repurposing existing FDA-approved drugs for other cancers. The most promising trials include the use of Tumor Treating Fields (TTF), a mitochondrial inhibitor (CPI-613), and a nanoparticle-delivered paclitaxel (EndoTAG-1). However, the likelihood of these trials significantly improving PDAC survival in the near term is low, given the historical success rates of drug development in pancreatic cancer.
The study underscores the challenges in PDAC research, including the high cost and time required for drug development, the low probability of success, and the need for diversification in research approaches beyond chemotherapy and immunotherapy. It also highlights the importance of early detection and the potential impact of discovering effective PDAC biomarkers. Despite the current limitations, the ongoing clinical trials offer hope for future advances in PDAC treatment, emphasizing the need for continued investment and innovation in this challenging field.
