Fruquinitinib combined with nab-paclitaxel and gemcitabine (AG) as the first-line treatment for pancreatic ductal adenocarcinoma (PDAC) with liver metastases: An open-label, single-arm, single-center phase II clinical study

BackgroundPDAC with liver metastases remains a significant challenge with poor prognosis. While AG has emerged as a first-line standard treatment, the efficacy was not that satisfying. This trial aims to investigate the efficacy and safety of the combination of fruquintinib and AG on PDAC patients (pts) with liver metastases.MethodsPDAC pts with liver metastases, who had not received systemic therapy, aged ≥18 years, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 were included. Enrolled pts received fruquintinib 4mg po, d1-d14, gemcitabine 1000 mg/m2, i.v and d1, 8, 15,nab-paclitaxel 125 mg/m2, i.v, d1,8,15, q4w. The primary endpoint was objective response rate (ORR, RECIST 1.1), and the secondary endpoints were progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and adverse events (AEs) etc.ResultsBetween Aug. 2021 and May 2023, a total of 30 pts were included. 26 pts were evaluable and the mean age was 58.7 years (30-73) and equal gender representation. The primary origin was in pancreatic head (42%), body/neck (35%), and tail (23%). 5 pts harbored distant metastases beyond the liver. 15 achieved partial response and 4 had stable disease, yielding a confirmed ORR of 57.7% (95% CI: 38.7%, 76.7%) and a DCR of 73.1% (95% CI: 56.0%, 90.1%). With a median follow-up time of 10 months (95% CI: 7-12), the median PFS reached 8 months (95% CI: 4-8) while the OS data was not yet mature for final analysis. 7 pts underwent surgery with R0 resections of primary lesion. The most frequent treatment-emergent AEs (TEAEs) included decreased WBC (100%), fatigue (88.46%), hyperglycaemia (84.62%), hypercholesterolaemia (73.08%), decreased PLT (69.23%), and hypertriglyceridaemia (46.15%). Grade 3/4 TEAEs were mainly decreased WBC, PLT, and RBC (each 11.5%). 2 (7.7%) pts experienced SAEs (gastrointestinal hemorrhage).ConclusionsThe combination of fruquintinib and AG regimen has demonstrated promising efficacy and tolerable toxicity in the first-line treatment of PDAC with liver metastases and holds potential as a conversion therapy strategy for these pts.Clinical trial identificationNCT05168527.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.