Perioperative Modified FOLFIRINOX Shows Promise for Pancreatic Cancer

According to a nonrandomized phase 2 trial, the use of modified FOLFIRINOX perioperatively was safe and effective among patients with resectable pancreatic cancer, showing a clinically meaningful improvement in survival when compared with historical controls.

There are approximately 15% to 20% of patients with pancreatic ductal adenocarcinoma (PDAC) who present with surgically resectable disease — potentially curable with surgery and adjuvant chemotherapy. The standard of care for this adjuvant chemotherapy is 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). However, durable disease control is rare and, according to Michael Cecchini, MD, Yale University School of Medicine, New Haven, Connecticut and coauthors, “most patients with resectable PDAC will develop recurrent disease and ultimately die of advanced PDAC.”

In this single-arm, open-label, nonrandomized phase 2 study, 46 patients with untreated unresectable pancreatic ductal adenocarcinoma were enrolled and treated with 6 cycles of neoadjuvant modified FOLFIRINOX, followed by surgical resection and 6 cycles of adjuvant modified FOLFIRINOX. Also performed were circulating tumor DNA (ctDNA) analysis and keratin 17 (K17) immunohistochemical detection. The primary end point was 12-month progression-free survival (PFS) — considered to be statistically significant if greater than 50%, the historical control (with adjuvant gemcitabine, standard of care at this time). Additional end points included overall survival (OS), ctDNA level, and K17 tumor levels.

Of the 46 patients enrolled, 80% completed the 6 perioperative cycles of modified FOLFIRINOX, and 72% underwent surgery. Of the 33 patients who underwent surgery, 27 had resection per protocol (R0, n = 25; R1, n = 2) while 6 patients were identified with metastatic or unresectable disease upon resection. An additional 10 patients underwent surgery off protocol. The 12-month PFS of the intention-to-treat population was 67%, with a median PFS of 16.6 months. The median OS was 37.2 months. Those patients who had detectable ctDNA levels at 4 weeks following surgery had worse PFS (hazard ratio [HR], 34.0; P = .006) and OS (HR, 11.7; P = .02) compared to patients with undetectable levels. Those patients with high K17 expression had worse PFS (HR, 2.7; P = .09) and OS (HR, 3.2; P = .07), but not to a degree of statistical significance.

Dr Cecchini et al concluded perioperative modified FOLFIRINOX was feasible and safe among patients with resectable pancreatic ductal adenocarcinoma, yielding “exceptional survival with high R0 resection rates for patients who completed per-protocol therapy.” They added that ctDNA and K17 could prove to be promising biomarkers for treatment of this disease with this regimen. Further studies are needed to determine the role of these potential biomarkers, and to better evaluate this regimen against adjuvant FOLFIRINOX.

Source:

Cecchini M, Salem RR, Robert M, et al. Perioperative modified FOLFIRINOX for resectable pancreatic cancer: A nonrandomized controlled trial. JAMA Oncol. Published online: June 20, 2024. doi:10.1001/jamaoncol.2024.1575