First-line nanoparticle polymeric micellar paclitaxel with gemcitabine in metastatic pancreatic cancer: a single-arm, prospective, and exploratory study

Background: Pancreatic cancer is one of the most lethal malignancies, with limited therapeutic options. In this exploratory trial, we aimed to evaluate the efficacy and safety of nanoparticle polymeric micellar paclitaxel (pm-Pac) combined with gemcitabine as first-line treatment for metastatic pancreatic cancer (mPC). Methods: Twenty-one patients with histologically or cytologically confirmed mPC were enrolled in this study. The primary endpoint was progression-free survival (PFS). Meanwhile, the secondary endpoints included the objective response rate (ORR), overall survival, disease control rate (DCR), duration of response (DOR), and safety of combination therapy. Results: The median PFS was 7.4 months (95% confidence interval CI: 5.4-9.4 months). The ORR and DCR were 52.4% (95% CI: 29.1%-75.7%) and 95.2% (95% CI: 85.3%-100%), respectively. Amongst patients who achieved partial response, the median DOR was 4.8 months (95% CI: 1.5-8.1 months). No treatment-related deaths were reported. Grade 3-4 adverse events (AEs) occurred in 81.0% of patients, with increased γ-glutamyltransferase levels (38.1%), neutropenia (33.3%), and leukocytopenia (28.6%) being the most frequent AEs. Low SERPINB3 and SERPINB4 expression was correlated with prolonged PFS, accompanied by the significant downregulation of gene sets involved in DNA replication, nonsense-mediated mRNA decay, and protein translation in long-PFS tumours. Tumour immune microenvironment analysis revealed that patients with short PFS had increased levels of common lymphoid progenitors and decreased populations of mature B and T lymphocytes. Conclusions: The combination of pm-Pac and gemcitabine as first-line therapy for mPC exhibited favourable tolerability and clinical efficacy. However, larger randomized-controlled trials are needed to validate these preliminary findings. Trial Registration: www.chictr.org.cn, ChiCTR2300078861.