Similar progression-free survival was found with gemcitabine/nab-paclitaxel vs modified leucovorin, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC), but less toxicity, according to findings from the phase II PASS-01 trial reported in the Journal of Clinical Oncology.
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 either gemcitabine/nab-paclitaxel (n = 80) or mFOLFIRINOX (n = 80). Patients with germline pathogenic variants in BRCA1/2 or PALB2 were excluded from the trial. The per-protocol population of patients who received at least one dose of chemotherapy included 71 from the mFOLFIRINOX group and 69 from 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 with mFOLFIRINOX vs gemcitabine/nab-paclitaxel, respectively (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 with mFOLFIRINOX vs gemcitabine/nab-paclitaxel, respectively, 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. Treatment-related toxicities 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. Toxicities 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, led by Jennifer J. Knox, MD, MSc, FRCPC, of McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, 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.”
Knox JJ et al: J Clin Oncol 43:3355-3368, 2025.
