TOPLINE:

Among patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, neoadjuvant FOLFIRINOX showed comparable overall survival to neoadjuvant gemcitabine-based chemoradiotherapy, suggesting that either regimen may be considered for these patients.

METHODOLOGY:

• Upfront surgery with adjuvant chemotherapy has long been the standard of care for patients with resectable or borderline resectable pancreatic cancer. However, nearly half are unable to receive postoperative systemic therapy due to surgery complications or frailty. The PREOPANC trial demonstrated a survival benefit with neoadjuvant gemcitabine-based chemoradiotherapy over upfront surgery. Meanwhile, FOLFIRINOX has shown superiority over gemcitabine in other settings.
• The PREOPANC-2 trial evaluated whether neoadjuvant FOLFIRINOX improved overall survival compared with neoadjuvant gemcitabine-based chemoradiotherapy among patients with resectable or borderline resectable pancreatic ductal adenocarcinoma. Patients (N = 369) were randomly assigned to receive either neoadjuvant FOLFIRINOX (n = 185) or gemcitabine-based neoadjuvant chemoradiotherapy (CRT group; n = 184).
• Patients in the FOLFIRINOX group received eight cycles of FOLFIRINOX (intravenous 85 mg/m² oxaliplatin, 180 mg/m² irinotecan, 400 mg/m² leucovorin, 400 mg/m² fluorouracil bolus, and 2400 mg/m² continuous infusion of fluorouracil over 46 hours every 14 days), followed by surgery without adjuvant treatment.
• Patients in the CRT group received three cycles of gemcitabine (1000 mg/m² intravenously on days 1, 8, and 15 of each 28-day cycle and on days 1 and 8 only for cycles 1 and 3) combined with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and four cycles of adjuvant gemcitabine.

TAKEAWAY:

• After a median follow-up of 42 months, 70% (258 of 369) of patients had died (68% in the FOLFIRINOX group and 72% in the CRT group). Median overall survival was 21.9 months in the FOLFIRINOX group vs 21.3 months in the CRT group (hazard ratio [HR], 0.88; P = .32). Similarly, progression-free survival did not differ significantly between the groups (median, 12.1 vs 11.9 months; HR, 0.84; P = .14).
• For patients with resectable disease, median overall survival was similar with either neoadjuvant FOLFIRINOX or CRT (21.5 vs 22.5 months; HR, 0.93; P = .64). For those with borderline resectable disease, FOLFIRINOX yielded longer survival, but the difference was not statistically significant (23.4 vs 17.0 months; HR, 0.80; P = .30).
• After neoadjuvant treatment, 84% of patients in the FOLFIRINOX group vs 90% of those in the CRT group underwent surgery (P = .090), with disease progression being the most common reason for not proceeding to surgery. Resection rates were similar (77% vs 75%; P = .69). as were R0 resection rates (60% vs 67%; P = .25).
• Adverse events of grade 3 or higher occurred in 67% of patients in the FOLFIRINOX group and 60% of those in the CRT group. The most common grade 3-4 events were neutropenia (25% of patients in the FOLFIRINOX group vs 22% of patients in the CRT group), diarrhea (23% vs 1%), and leukopenia (8% vs 15%). There were two treatment-related deaths in the FOLFIRINOX group and one in the CRT group.

IN PRACTICE:

“In view of the results, both neoadjuvant treatment regimens may be considered in patients with resectable or borderline resectable [pancreatic ductal adenocarcinoma] based on individual patient characteristics,” the authors wrote. That approach, they noted, offers a valuable alternative to patients for whom FOLFIRINOX, the generally preferred regimen, is not suitable. 

SOURCE:

The study, led by Quisette P. Janssen, MD, and Jacob L. van Dam, MD, Erasmus MC Cancer Institute in Rotterdam, Netherlands, was published online in The Lancet Oncology.

LIMITATIONS:

The study population was heterogeneous, including both resectable and borderline resectable cases, which may have affected subgroup analyses. No centralized review of radiologic or pathologic data was performed. Toxicity in the FOLFIRINOX group may have been increased due to the use of a full-dose rather than modified-dose regimen, as used in other recent trials.

DISCLOSURES:

The study received funding from the Dutch Cancer Society and ZonMw. Several authors reported receiving grants or honoraria and having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.