Neoadjuvant modified FOLFIRINOX followed by postoperative gemcitabine in borderline resectable pancreatic adenocarcinoma: a Phase 2 study for clinical and biomarker analysis

Changhoon Yoo,Jae Hoon Lee,Sang Soo Lee,Seung Soo Lee,Dae Wook Hwang,Jae Ho Jeong,Jin Hee Kim,Jaewon Hyung,Heung-Moon Chang,Dong Wan Seo,Tae Jun Song,Ki Byung Song,Hyung‐Seung Jin ,Woo Hyung Lee ,Myung–Hwan Kim ,Jin‐Hong Park ,Baek‐Yeol Ryoo ,Kyu-Pyo Kim,Do Hyun Park,Sung Koo Lee,Song Cheol Kim

doi:10.1038/s41416-020-0867-x

Abstract

BackgroundPatients with borderline resectable pancreatic cancer (BRPC) have poor prognosis with upfront surgery.MethodsThis was a single-arm Phase 2 trial for clinical and biomarker analysis. The primary endpoint is 1-year progression-free survival (PFS) rate. Patients received 8 cycles of neoadjuvant modified (m) FOLFIRINOX. Up to 6 cycles of gemcitabine were given for patients who underwent surgery. Plasma immune cell subsets were measured for analysing correlations with overall survival (OS).ResultsBetween May 2016 and March 2018, 44 chemotherapy- and radiotherapy-naïve patients with BRPC were included. With neoadjuvant mFOLFIRINOX, the objective response rate was 34.1%, and curative-intent surgery was done in 27 (61.4%) patients. With a median follow-up duration of 20.6 months (95% confidence interval [CI], 19.7–21.6 months), the median PFS and OS were 12.2 months (95% CI, 8.9–15.5 months) and 24.7 months (95% CI, 12.6–36.9), respectively. The 1-year PFS rate was 52.3% (95% CI, 37.6–67.0%). Higher CD14+ monocyte (quartile 4 vs 1–3) and lower CD69+ γδ T cell (γδ TCR+/CD69+) levels (quartiles 1–3 vs 4) were significantly associated with poor OS (p = 0.045 and p = 0.043, respectively).ConclusionsNeoadjuvant mFOLFIRINOX followed by postoperative gemcitabine were feasible and effective in BRPC patients. Monocyte and γδ T cells may have prognostic implications for patients with pancreatic cancer. ClinicalTrials.gov identifier: NCT02749136.

Highlights

Patients with borderline resectable pancreatic cancer (BRPC) have poor prognosis with upfront surgery
There is no evidence based on randomised Phase 3 trials investigating BRPC or locally advanced unresectable pancreatic cancer (LAUPC), conventional or modified FOLFIRINOX has been widely used as neoadjuvant therapy based on its success with metastatic pancreatic cancer patients.[6]
We investigated the efficacy and safety of perioperative chemotherapy consisting of neoadjuvant modified FOLFIRINOX and postoperative gemcitabine for patients with BRPC

Summary

Introduction

Patients with borderline resectable pancreatic cancer (BRPC) have poor prognosis with upfront surgery. Surgery is the only curative treatment option for resectable disease, 5-year survival rates after resection remain poor between at 15 and 30%.2–4. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAUPC) are anatomically characterised by the involvement extent of major vessels, which is likely associated with positive resection margin.[5] BRPC has been regarded as a potentially curative disease, and neoadjuvant therapy may lead to improvements in R0 resection rates and long-term survival. There is no evidence based on randomised Phase 3 trials investigating BRPC or LAUPC, conventional or modified FOLFIRINOX has been widely used as neoadjuvant therapy based on its success with metastatic pancreatic cancer patients.[6] the optimal duration of preoperative chemotherapy, regimens of postoperative chemotherapy, and biomarkers for the prediction of prognosis have not yet been defined

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Conclusion