In a phase II trial (PASS-01) reported in the Journal of Clinical Oncology, Knox et al found similar progression-free survival with modified leucovorin, fluorouracil, irinotecan, oxaliplatin (mFOLFIRINOX) vs gemcitabine/nab-paclitaxel in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC).
Study Details
In the open-label trial, 160 patients (intention-to-treat [ITT] population) from sites in Canada and the United States were randomly assigned between October 2020 and January 2024 to receive mFOLFIRINOX (n = 80) or gemcitabine/nab-paclitaxel (n = 80). Patients with germline pathogenic variants in BRCA1/2 or PALB2 were excluded from the trial. The per-protocol population (those who received at least one dose of chemotherapy) consisted of 71 patients in the mFOLFIRINOX group and 69 in the gemcitabine/nab-paclitaxel group. The primary outcome measure was progression-free survival in the ITT population.
Study Findings
Median follow-up was 8.3 months (range = 0.3–37.2 months). In the ITT population, median progression-free survival was 4.0 months in the mFOLFIRINOX group vs 5.3 months in the gemcitabine/nab-paclitaxel group (hazard ratio [HR] = 1.37, 95% confidence interval [CI] = 0.97–1.92, P = .069). In the per-protocol population, median progression-free survival was 4.2 months in the mFOLFIRINOX group vs 5.3 months in the gemcitabine/nab-paclitaxel group (HR = 1.33, 95% CI = 0.93–1.90, P = .114).
In the ITT population, median overall survival was 8.5 months in the mFOLFIRINOX group vs 9.7 months in the gemcitabine/nab-paclitaxel group (HR = 1.57, 95% CI = 1.08–2.28, P = .017). In the per-protocol population, median overall survival was 8.7 vs 10.3 months (HR = 1.59, 95% CI = 1.07–2.36, P = .021).
Among patients in the mFOLFIRINOX group vs the gemcitabine/nab-paclitaxel group with available data, median progression-free survival was 3.0 vs 5.5 months in patients with basal-like PDAC (P = .17) and 6.3 vs 5.4 months in those with classical PDAC (P = .36). Median overall survival was 7.5 vs 8.9 months in patients with basal-like PDAC (P = .75) and 9.7 vs 13.9 months in those with classical PDAC (P = .047).
In the per-protocol population, hospital admission for treatment-related toxicities occurred in 14 patients (20%) in the mFOLFIRINOX group and 5 (7%) in the gemcitabine/nab-paclitaxel group. Those in the mFOLFIRINOX group consisted of gastrointestinal-related complications in seven patients, febrile neutropenia in three, and pneumonia, acute renal failure, pulmonary embolism, and cerebellar stroke in one each. Those in the gemcitabine/nab-paclitaxel group consisted of severe fatigue in two patients and nausea, cellulitis, and acute renal failure in one each.
In total, 75 patients (54%) received second-line treatment, including correlate-guided treatment in 33. Median time on second-line treatment was 2.1 months. Median overall survival was 5.4 months with correlate-guided treatment vs 4.4 months with a standard chemotherapy approach (P = .45).
The investigators concluded: “In the phase II…PASS-01 trial population, [progression-free survival] was similar between [gemcitabine/nab-paclitaxel] and [mFOLFIRINOX]; however, [overall survival] and safety trends favored [gemcitabine/nab-paclitaxel]. The second-line setting appears inadequate to offer precision choices, given the short survival observed.”
Jennifer J. Knox, MD, MSc, of McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Stand Up to Cancer PASS-01 Trial Grant, Ontario Institute for Cancer Research, and others. For full disclosures of all study authors, visit ascopubs.org.
