Neoadjuvant chemotherapy does not provide a survival benefit over upfront surgery in resectable pancreatic cancer, according to research presented at the 2023 ASCO Annual Meeting.
In a phase 2 trial, researchers found that patients who received neoadjuvant fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) had similar overall survival (OS) as patients who were treated with surgery upfront.
“[R]esults of this trial do not support neoadjuvant FOLFIRINOX as standard of care in resectable pancreatic cancer,” said study presenter Knut Jørgen Labori, MD, PhD, of Oslo University Hospital in Norway.
The trial included 140 patients with resectable pancreatic cancer who were treated at 12 centers in Norway, Sweden, Denmark, and Finland from 2017 through 2021.
The patients were randomly assigned to receive either 4 cycles of neoadjuvant FOLFIRINOX followed by surgery and 8 cycles of adjuvant modified FOLFIRINOX (n=77) or upfront surgery and 12 cycles of adjuvant modified FOLFIRINOX (n=63).
In the neoadjuvant arm, 64 patients started neoadjuvant FOLFIRINOX, 40 completed it, 63 underwent resection, and 51 started adjuvant chemotherapy. In the upfront surgery arm, 56 patients underwent resection, and 47 started adjuvant chemotherapy.
In the intent-to-treat population, the median OS was 25.1 months in the neoadjuvant FOLFIRINOX arm and 38.5 months in the upfront surgery arm (hazard ratio [HR], 1.52; 95% CI, 0.94-2.46; P =.096). The proportion of patients who were still alive at 18 months was 60% and 73%, respectively (P =.100).
Among patients treated per protocol, the median OS was 23.0 months in the neoadjuvant arm and 34.4 months in the upfront surgery arm (HR, 1.46; 95% CI, 0.89-2.41; P =.158). The per-protocol population included 55 patients from the upfront surgery arm who had surgical exploration and 60 patients who received at least 1 cycle of neoadjuvant FOLFIRINOX.
In the per-protocol population, the R0 resection rate was 59% in the neoadjuvant arm and 33% in the upfront surgery arm (P =.011). In the intent-to-treat population, the R0 resection rate was 56% and 39%, respectively (P =.076).
Dr Labori noted that additional follow-up may better elucidate the long-term effects of the improvement in R0 resection in the neoadjuvant arm.
The safety population included 120 patients who received at least 1 dose of neoadjuvant chemotherapy and/or adjuvant chemotherapy. The rate of grade 3-5 adverse events (AEs) was 55.6% among patients who received neoadjuvant FOLFIRINOX, 39.2% among patients in the neoadjuvant arm who received adjuvant chemotherapy, and 40.4% in patients in the upfront surgery arm who received adjuvant chemotherapy.
Common grade 3-5 AEs among patients who received neoadjuvant chemotherapy were diarrhea (19.7%), nausea and vomiting (14.8%), and neutropenia (11.5%). There were 2 grade 5 AEs in the neoadjuvant arm — 1 sudden death 8 days after the first cycle of FOLFIRINOX and 1 COVID-19-related death 61 days after the first cycle.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Labori KJ, Bratlie OS, Biörserud C, et al. Short-course neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer: a multicenter randomized phase-II trial (NORPACT-1). ASCO 2023. June 2-6, 2023. Abstract LBA4005.