Total Neoadjuvant Therapy Improves R0 Resection Rate in Borderline Resectable Pancreatic Adenocarcinoma

For patients with localized pancreatic adenocarcinoma with some degree of vascular involvement (as defined by National Comprehensive Cancer Network [NCCN]), termed borderline resectable, management has been heterogeneous and includes neoadjuvant chemoradiation, surgery, and most recently, neoadjuvant therapy. Retrospective data indicate that neoadjuvant chemotherapy can improve rates of R0 resection in patients with borderline resectable disease. In metastatic setting, use of the FOLFIRINOX regimen (fluorouracil, irinotecan, and oxaliplatin) is associated with significant improvements in overall response rate (ORR) and overall survival (OS), compared to gemcitabine. The use of radiotherapy in pancreatic cancer is controversial but is included in some guidelines for borderline resectable disease.

In an attempt to improve R0 resectability and chance of cure, total neoadjuvant therapy with FOLFIRINOX followed by patient personalized chemoradiation in patients with borderline resectable pancreatic cancer was prospectively evaluated in 48 patients in a single-arm, phase II trial at Massachusetts General Hospital. Patients (ECOG performance status 0 or 1) with newly diagnosed pancreatic adenocarcinoma considered borderline resectable by a multidisciplinary team received 8 cycles of neoadjuvant FOLFIRINOX followed by either short- or long-course chemoradiotherapy. Patients with resolution of vascular involvement (56%) received short-course chemoradiotherapy (either protons or photons) with capecitabine; patients with persistent vascular involvement (35%) received long-course chemoradiotherapy with fluorouracil or capecitabine.

A total of 31 patients (65%) achieved R0 resection, and of the 32 patients who underwent surgical resection, 31 had an R0 resection (97%). The median progression-free survival (PFS) in the entire population was 14.7 months, with a 2-year PFS rate of 43%. The median OS was 37.7 months, with a 2-year OS rate of 56%. In the 32 patients who underwent resection, the median PFS was 48.6 months, and OS has not been reached. The 2-year PFS and OS rates were 55% and 72%, respectively.

FOLFIRINOX induction therapy was associated with grade 3 or higher adverse events (AEs) in 19% of patients. The most common severe AEs were diarrhea (5 patients), neutropenia (2 patients), and peripheral neuropathy (2 patients).

The investigators concluded that neoadjuvant therapy with FOLFIRINOX followed by individualized chemoradiation results in high rates of R0 resection and prolonged PFS and OS in patients with borderline resectable pancreatic cancer. These data support the ongoing phase III Alliance A021501 trial, which is evaluating neoadjuvant chemotherapy with or without radiation therapy in patients with borderline resectable pancreatic cancer.

JAMA Oncol. 2018 May 3 [Epub ahead of print].

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