Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results

Area of Science:

• Oncology
• Immunotherapy
• Surgical Oncology

Background:

• Pancreatic ductal adenocarcinoma (PDAC) presents late and recurs early, with limited systemic therapy options.
• PDAC features an immunosuppressive tumor microenvironment, leading to poor immunotherapy response in metastatic settings.
• Neoadjuvant immunotherapy is being investigated to enhance immune response against micrometastatic disease and prevent recurrence.

Purpose of the Study:

• To conduct a scoping review identifying published and ongoing trials of preoperative immunotherapy for PDAC.
• To summarize the landscape of neoadjuvant immunotherapy agents and combinations being studied.
• To assess the potential of neoadjuvant immunotherapy to improve outcomes in PDAC.

Main Methods:

• A scoping review methodology was employed.
• Searched for published and ongoing clinical trials investigating preoperative immunotherapy in PDAC.
• Identified 9 published and 27 ongoing trials.

Main Results:

• Published trials included immune checkpoint inhibitors, cancer vaccines, and other immune-modulating agents.
• Most published trials are early-phase, suggesting improved disease-free and overall survival when combined with standard neoadjuvant therapy.
• Ongoing trials are evaluating various combinations of immunotherapy agents with chemotherapy and/or radiation.

Conclusions:

• Rational combination immunotherapy, alongside standard neoadjuvant therapy, holds potential for improving PDAC outcomes.
• Further clinical trials are necessary to validate these findings.
• Adaptive trial designs are recommended for future investigations.