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Preoperative modified FOLFIRINOX shows efficacy as a reference regimen for future trials in borderline resectable adenocarcinoma of the pancreas

The optimal preoperative regimen for patients with borderline resectable ductal adenocarcinoma of the pancreas is subject to debate. In order to set a reference for future clinical trials in this setting, the phase II Alliance A021501 trial evaluated and compared a modified FOLFIRINOX (mFOLFIRINOX) regimen to mFOLFIRINOX + radiotherapy as a preoperative therapy for these patients.


ASCO guidelines currently recommend preoperative therapy in patients with pancreatic cancer whose primary tumor has radiographic interface with mesenteric vasculature, as these patients are at high risk of a margin-positive resection. While preoperative chemotherapy with or without radiotherapy is common, the optimum regimen in this setting is controversial.

Designed to establish a reference regimen for future clinical trials, the Alliance A021501 phase II trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) into two treatment arms: 8 cycles of neoadjuvant mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 over 46 hours) (Arm A; N= 70) or 7 cycles of mFOLFIRINOX, followed by stereotactic body RT (SBRT, 33-40 Gy in 5 fractions [fx]) or hypofractionated image guided RT (HIGRT, 25 Gy in 5 fx) (Arm B; N= 56). In both arms, patients without disease progression subsequently underwent a pancreatectomy, followed by 4 cycles of adjuvant FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 over 46 hours). Evaluated separately in each arm, the primary endpoint was 18-month overall survival rate, with secondary endpoints of event-free survival (EFS), adverse events, resection rate and pCR rate. A planned interim analysis dictated the closure of whichever arm in which ≤11 of the first 30 patients underwent a R0 resection. This resulted in the closure of arm B.At the time of this interim analysis, 33% of patients in Arm B had undergone a R0 resection, as compared to 57%  in arm A.

Two thirds of patients treated with preoperative mFOLFIRINOX still alive at 18 months

At a median follow-up of 27 and 31 months respectively, the median OS in arms A & B were 29.8 months and 17.1 months. The corresponding 18-month OS rates were reported at 66.4% and 47.3% in arms A and B, respectively. Among patients who underwent a pancreatectomy the 18-month OS rates were markedly higher at of 93.1% and 78.9%, respectively. The median EFS reached 15.0 months in arm A as compared to 10.2 months in arm B.

Arm A had a resection rate of 49% as compared to 35% in arm B. Overall, 88% of arm A patients underwent an R0 resection as compared to 74% of arm B patients. Conversely, pathological complete responses were not seen in arm A as compared to 11% in arm B. Dose reductions occured in 60% of arm A patients, and in 75% of arm B patients, while dose omissions occurred in 14% and 15% of patients, respectively. Grade 3 adverse events (AEs) were experienced by 57% of patients in arm A, and in 64% of patients in arm B, with grade 4 AEs occurring at least once in 17% and 9% of patients in each arm, respectively.


In conclusion, preoperative mFOLFIRINOX produced an OS benefit comparable with historical data in this setting. With arm B meeting the predefined futility boundary, mFOLFIRINOX represents a reference preoperative regimen for patients with BR PDAC.


Katz HG M et al., Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX plus hypofractionated radiation therapy (RT) for borderline resectable (BR) adenocarcinoma of the pancreas. Presented at ASCO GI 2021; Abstract 377.

Speaker Matthew HG Katz

Matthew HG Katz

Matthew HG Katz, MD, FACS, FASCO, MD Anderson Cancer Center, Houston, Texas, United States


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