Background
Phase II pilot trial (Alliance A021101). 22 patients with borderline resectable pancreatic cancer at 4 ALLIANCE sites. Designed to evaluate the feasibility of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by stereotactic body radiotherapy (SBRT) and surgical resection.
Interventions and follow up
Arm A: mFOLFIRINOX × 4 cycles → SBRT 33 Gy in 5 fractions → surgical resection 4–8 weeks post-SBRT
Primary endpoint: Feasibility (proportion completing all preoperative therapy and undergoing resection attempt)
mFollow up: 21 month
Primary endpoint: Feasibility (proportion completing all preoperative therapy and undergoing resection attempt)
mFollow up: 21 month
Results
Resection rate: 68% (15/22)
R0 resection: 93% of resected patients (12/15 pancreatectomies with negative margins)
mOS: 21.7 months (all enrolled)
1-yr OS: 67%
R0 resection: 93% of resected patients (12/15 pancreatectomies with negative margins)
mOS: 21.7 months (all enrolled)
1-yr OS: 67%
Adverse events
Main adverse events: Grade ≥3 AEs during preoperative mFOLFIRINOX: 52%. Grade ≥3 SBRT toxicity: none. Postoperative complications in 67% of resected patients (similar to historical rates).
Conclusions
Preoperative mFOLFIRINOX followed by SBRT and resection for borderline resectable pancreatic cancer is feasible, with 93% R0 resection rates in those who underwent surgery. The pilot trial established the regimen for evaluation in a phase III Alliance A021501 trial.
Key Limitations
Key Limitations: Small pilot trial (n=22), no control arm. Feasibility endpoint, not powered for efficacy. High rate of perioperative complications. Heterogeneous patient selection (some locally advanced tumors included). SBRT technique may not reflect all institutional practices. OS data immature at time of initial report.
Clinical Context
Alliance A021101 established proof of concept for intensified neoadjuvant mFOLFIRINOX + SBRT in BRPC, informing the design of Alliance A021501 (SBRT vs hypofractionated RT in BRPC). Current NCCN guidelines recommend preoperative therapy for BRPC; mFOLFIRINOX-based regimens are preferred for eligible patients. Alliance A021806 is now testing neoadjuvant mFOLFIRINOX vs adjuvant mFOLFIRINOX in resectable disease.
References
References: Katz MH et al, JAMA Surg 2016 (Alliance A021101)