According to findings from a randomized phase II trial reported by Bai et al in the Journal of Clinical Oncology, treatment with the immunochemotherapy combination of the PD-1 inhibitor toripalimab and modified FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and fluorouracil) significantly improved event-free survival in patients with borderline resectable or locally advanced pancreatic cancer.
Study Details
The single-center, open-label trial enrolled 392 patients with histologically or cytologically confirmed pancreatic ductal adenocarcinoma between April 2019 and March 2025. Eligible patients were aged 18 to 75 years, had borderline resectable or locally advanced disease, and had an Eastern Cooperative Oncology Group performance status of 0 or 1.
Patients were randomly assigned to receive modified FOLFIRINOX plus toripalimab (immunochemotherapy, n = 196) or modified FOLFIRINOX alone (chemotherapy, n = 196). Toripalimab was administered intravenously at 3 mg/kg every 2 weeks; modified FOLFIRINOX was administered every 2 weeks.
Treatment response and surgical eligibility were assessed every 2 months, with resection decisions made by a multidisciplinary team. The primary endpoint was event-free survival in the intention-to-treat population. Secondary endpoints included overall survival, objective response rate, tumor resection rate, R0 resection rate, and safety.
Key Results
After a median follow-up of 39.6 months, median event-free survival was 11.1 months with immunochemotherapy vs 9.6 months with chemotherapy alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.60–0.92; P = .007). The 3-year event-free survival rates were 13.6% and 7.5%, respectively. Median overall survival was 20.6 vs 17.1 months (HR = 0.81, 95% CI = 0.63–1.03; P = .080).
Prespecified subgroup analyses suggested that the benefit was primarily confined to patients with borderline resectable disease. In this subgroup, median event-free survival was 12.7 vs 9.6 months (HR = 0.66, 95% CI = 0.46–0.95; P = .023), and median overall survival was 25.9 vs 16.2 months (HR = 0.64, 95% CI = 0.43–0.96; P = .032). No significant survival differences were observed among patients with locally advanced disease.
The objective response rate was higher with immunochemotherapy (30.1% vs 18.9%; P = .010), although tumor resection rates were similar (42.3% vs 43.9%). Among evaluable patients who underwent resection, R0 resection rates were 84.1% and 74.7%, respectively (P = .178).
Grade 3 or higher adverse events occurred in 47.9% of patients receiving immunochemotherapy and 49.2% receiving chemotherapy alone. Neutropenia was the most common severe adverse event (35.6% vs 36.4%). Among patients undergoing resection, grade 3 or higher postoperative complications occurred in 30.1% and 25.6%, respectively.
The investigators concluded: “The addition of PD-1 blockade to modified FOLFIRINOX significantly improved [event-free survival] without increasing treatment-related toxicity or surgical morbidity in patients with [borderline resectable pancreatic cancer] or [locally advanced pancreatic cancer].”
Tingbo Liang, MD, PhD, of the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; and Cancer Center, Zhejiang University, Hangzhou, China, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Key Research and Development Program of China and others. For full disclosures of the study authors, visit ascopubs.org.
