Seo Yongwoo David, Katz Matthew H G, Snyder Rebecca A
Division of Surgery, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Surg Oncol. 2025 Apr;32(4):2777-2785. doi: 10.1245/s10434-024-16840-2. Epub 2025 Jan 15.
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.
尽管全身治疗和多模式治疗不断取得进展，但胰腺癌的预后仍然很差。本综述分析了胰腺癌临床试验的最新进展和未来方向，强调了从传统方法向更个性化和生物驱动的治疗模式的演变。虽然围手术期治疗已使总生存期有所改善，但我们对最佳治疗策略的理解仍存在差距。关键问题包括特定化疗药物的选择、术前治疗的持续时间、放疗的作用以及对治疗反应的准确和实时评估。从历史上看，胰腺癌临床试验是根据解剖学标准设计的，没有考虑到这种疾病固有的生物异质性。该领域目前正朝着精准肿瘤学方法发展，利用基因组和转录组数据来识别预测性生物标志物并个性化治疗选择。新型临床试验设计，如平台试验和篮子试验，正在加速对新治疗策略的评估，并促进有效的患者选择，特别是在新出现的靶向治疗如KRAS抑制剂的背景下。此外，实施动态反应评估技术，如循环肿瘤DNA和放射组学，可能为治疗决策提供信息，并改善对长期结果的预测。通过整合这些不断发展的策略，新兴的临床试验格局有可能改变胰腺癌的治疗方式，并在患者预后方面取得有意义的改善。
