Preoperative Nivolumab Plus Modified FOLFIRINOX Shows Potential in Borderline-Resectable Pancreatic Cancer

Preoperative immunotherapy combined with chemotherapy was well tolerated in patients with borderline-resectable pancreatic cancer in a single-arm Phase 1b/2 clinical trial. The study enrolled 28 patients and evaluated nivolumab with modified FOLFIRINOX prior to surgery to investigate whether the combination could improve the likelihood of successful surgical resection and overall patient outcomes.

Among the patients, 79% proceeded to surgery, and all who underwent resection achieved complete tumor removal. Surgical margins were negative in 86%, and half of these patients displayed no detectable cancer within their lymph nodes at the time of surgery. Approximately 9% demonstrated a complete pathological response, while another 9% exhibited near-complete responses.

The immunotherapeutic agent employed was nivolumab, an immune checkpoint inhibitor targeting the PD-1 receptor. The chemotherapy regimen was modified FOLFIRINOX, which consists of fluorouracil, leucovorin, irinotecan, and oxaliplatin.

By administering combined therapy in the neoadjuvant setting, researchers obtained tumor tissue from surgical specimens for analyses including gene expression profiling, immunohistochemistry, and spatial transcriptomics. The integrated immune profiling revealed that the introduction of nivolumab alongside chemotherapy significantly boosted immune activation within the tumor microenvironment, evidenced by elevated infiltration of CD8+ cytotoxic T lymphocytes.

The treatment also appeared to induce disorganization within immune cell clusters and fostered an accumulation of plasma cells and exhausted T cells. Although the overall survival rates in this cohort did not significantly surpass historical controls treated with chemotherapy alone, the study found that a distinct subset of patients experienced profound and sustained tumor regression.