As reported in JAMA Oncology by Matthew H.G. Katz, MD, and colleagues, the National Clinical Trials Network phase II A021501 trial has shown better survival outcomes with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX; oxaliplatin, irinotecan, leucovorin, fluorouracil) vs mFOLFIRINOX plus hypofractionated radiotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma.
Matthew H.G. Katz, MD
As stated by the investigators, “National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma, but the optimal strategy remains unclear.”
Study Details
In the open-label multicenter trial, conducted between February 2017 and January 2019, 110 patients were randomly assigned to receive eight cycles of mFOLFIRINOX (oxaliplatin at 85 mg/m2, irinotecan at 180 mg/m2, leucovorin at 400 mg/m2, and infusional fluorouracil at 2,400 mg/m2 over 46 hours) every 2 weeks (n = 54) or seven cycles of mFOLFIRINOX followed by stereotactic body radiotherapy at 33 to 40 Gy in five fractions or hypofractionated image–guided radiotherapy at 25 Gy in five fractions (n = 56). At interim analysis, the radiotherapy group was closed, and an additional 16 patients were assigned to the mFOLFIRINOX-only group.
Patients without disease progression underwent pancreatectomy, followed by four cycles of postoperative FOLFOX6 (oxaliplatin at 85 mg/m2, leucovorin at 400 mg/m2, bolus fluorouracil at 400 mg/m2, and infusional fluorouracil at 2,400 mg/m2 over 46 hours).
The 18-month overall survival rate for each group was compared with a historical control rate of 50%. A planned interim analysis stipulated closure of a group in which 11 or fewer of the first 30 enrolled patients underwent R0 resection.
Key Findings
Among the first 30 evaluable patients enrolled in each group, 17 in the mFOLFIRINOX-only group (57%) and 10 in the mFOLFIRINOX-plus-radiotherapy group (33%) had undergone R0 resection, leading to closure of the latter group and continuation to full accrual in the former group.
Median follow-up was 42.9 months (95% confidence interval [CI] = 39.7–43.4 months). Among the first 62 evaluable patients with ≥ 18 months of follow-up in the mFOLFIRINOX group, 18-month overall survival was 66.7% (95% CI = 56.1%–79.4%); since the rate exceeded the 50% historical control rate, the regimen was deemed efficacious. Overall survival at 18 months in the mFOLFIRINOX-plus-radiotherapy group was 47.3% (95% CI = 35.8%–62.5%).
Among 65 vs 55 evaluable patients, median overall survival was 29.8 months (95% CI = 21.1–36.6 months) vs 17.1 months (95% CI = 12.8–24.4 months). Median event-free survival was 15.0 months (95% CI = 11.2–21.9 months) vs 10.2 months (95% CI = 6.7–17.3 months). Among the 32 vs 19 patients who underwent pancreatectomy, 18-month overall survival was 87.5% (95% CI = 70.0%–95.1) vs 78.9% (95% CI = 53.2%–91.5).
Grade ≥ 3 adverse events occurred in 57% vs 64% of patients.
The investigators concluded, “This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable overall survival in patients with borderline resectable pancreatic ductal adenocarcinoma compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting.”
Dr. Katz, of the Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
