Neoadjuvant mFOLFIRINOX Alone Yields Favorable Survival in Borderline Resectable PDAC

Treatment with modified folinic acid, fluorouracil (5-FU), irinotecan, and oxaliplatin (mFOLFIRINOX; arm 1) induced favorable survival compared with mFOLFIRINOX plus hypofractionated chemotherapy (arm 2) further justifying its use alone as a reference regimen in this setting.

According to findings from the phase 2 AO21501 trial (NCT02839343), the 18-month overall survival (OS) rate was 66.7% (95% CI, 56.1%-79.4%) in arm 1 compared with 47.3% in arm 2. Moreover, median OS was 29.8 months (95% CI, 21.1-36.6) and 17.1 months (95% CI, 12.8-24.4) in arms 1 and 2, respectively.

Patients in both arms received treatment with 85 mg/m² of oxaliplatin, 180 mg/m² of irinotecan, 400 mg/m² of leucovorin, and 2400 mg/m² of 5-FU every 2 weeks for 4 cycles. In arm 2, patients also received radiotherapy with a strong preference for stereotactic body radiotherapy (SBRT) where possible, consisting of 33 to 40 Gy in 5 fractions. Hypofractionated image-guided radiation therapy (HIGRT) was given at 25 Gy in 5 fractions. Following surgery, patients who had a performance status of 0 or 1 and no evidence of residual or recurrent disease then went on to receive 4 cycles of oxaliplatin at 85 mg/m², leucovorin at 400 mg/m², bolus 5-FU at 400 mg/m², and infusional 5-FU at 2400 mg/m² every 2 weeks.

At the time of the interim analysis, 120 patients were enrolled and randomly assigned to either arm 1 (n = 65) or arm 2 (n = 55). Patients in each respective arm received a median of 8 and 7 treatment cycles, respectively. Additionally, 87.5% of patients in the radiotherapy arm received SBRT and 12.5% received HIGRT. Additionally, the 49% of patients in arm 1 and 60% of patients in arm 2 had mFOLFIRINOX delays and dose omissions were necessary in 14% and 15% of patients in each group, respectively.

A total of 58% of patients in arm 1 and 51% of patients arm 2 underwent pancreatectomy on protocol. The median duration from last treatment with FOLFIRINOX or radiotherapy and surgery was 42 days and 44 days, respectively. Moreover, 34% of those in arm 1 and 24% of those in arm 2 received postoperative FOLFOX.

The trial had a median follow-up of 42.9 months. Additional findings from the study indicated that the median event-free survival was 15.0 months (95% CI, 11.2-21.9) vs 10.2 months (95% CI, 6.7-17.3) in each respective arm.

Grade 3 adverse effects (AE) were reported in 57% of patients in arm 1 compared with 64% in arm 2. Two patients in arm 1 experienced a grade 5 AE. Frequent grade 3 or higher AEs potentially associated with mFOLFIRINOX included diarrhea (18%), hypokalemia (17%), and neutropenia (12%). Anemia (5%) was the most common grade 3 or higher AE associated with radiotherapy.

Reference

Katz MHG, Shi Q, Meyers J, et al. Efficacy of preoperative mFOLFIRINOX vs mFOLFIRINOX plus hypofractionated radiotherapy for borderline resectable adenocarcinoma of the pancreas. JAMA Oncol. Published online July 14, 2022. doi:10.1001/jamaoncol.2022.2319