The Landmark Series: The Future of Pancreatic Cancer Clinical Trials.

Pancreatic cancer has a poor prognosis despite ongoing advances in systemic and multimodal therapies. This review analyzes recent progress and future directions in pancreatic cancer clinical trials, emphasizing the evolution from traditional approaches to a more personalized and biologically-driven treatment paradigm. While improvements in overall survival have been achieved through perioperative therapies, gaps remain in our understanding of optimal treatment strategies. Key questions include selection of specific chemotherapeutic agents, duration of preoperative therapy, the role of radiotherapy, and accurate and real-time assessment of response to therapy. Historically, pancreatic cancer clinical trials have been designed based on anatomic criteria, failing to account for the inherent biologic heterogeneity of this disease. The field is now moving towards a precision oncology approach, leveraging genomic and transcriptomic data to identify predictive biomarkers and personalize treatment selection. Novel clinical trial designs, such as platform and basket trials, are accelerating the evaluation of new therapeutic strategies and facilitating efficient patient selection, particularly in the context of new emerging targeted therapies such as KRAS inhibitors. Furthermore, implementation of dynamic response assessment techniques, such as circulating tumor DNA and radiomics, may inform treatment decision-making and improve prediction of long-term outcomes. By integrating these evolving strategies, the emerging clinical trial landscape has the potential to transform the treatment of pancreatic cancer and yield meaningful improvements in patient outcomes.