1638P - The prognostic and predictive role of class III β-tubulin and hENT1 expression in patients with advanced pancreatic ductal adenocarcinoma

Background

FOLFIRINOX and gemcitabine-nabpaclitaxel (GnP) are both standard first-line treatment regimens for advanced pancreatic ductal adenocarcinoma (PDAC), however, predictive biomarkers are currently lacking to guide treatment selection. We aimed to investigate the prognostic and predictive value of class III β-Tubulin (TUBB3) and human equilibrative nucleoside transporter 1 (hENT1) expression, which have previously been shown to be associated with taxane and gemcitabine resistance in advanced PDAC.

Methods

We conducted a retrospective analysis of 106 patients with advanced PDAC at Hacettepe University Cancer Institute. TUBB3 and hENT1 immunohistochemical staining were analyzed in tumor specimens and scored jointly according to the intensity of expression: high score (TUBB3^low/hENT1^high) and low score (TUBB3^high/hENT1^high, TUBB3^low/hENT1^low or TUBB3^high/hENT1^low). Response rates and progression-free survival (PFS) rates were compared based on TUBB3 and hENT1 expression.

Results

The median age was 60 years (range; 38-80 years) and 65% were male patients. The median progression-free survival (PFS) and overall survival (OS) of patients were 6.83 and 12.06 months, respectively. In patients who received the GnP regimen (n=68), a high combined score (TUBB3^low/hENT1^high) was associated with a higher disease control rate (DCR) (84.2% vs. 39.6%, p=0.001) and longer PFS (8.76 months vs. 3.1 months, p<0.001) compared to those with low score. In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR: 11.96; 95% CI: 2.61-54.82; p=0.001) and longer PFS (HR: 0.33; 95%CI: 0.18–0.60; p<0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving FOLFIRINOX regimen.

Conclusions

Our findings suggest that tumor TUBB3 and hENT1 expression may predict the efficacy of GnP regimen, and low TUBB3 and high hENT1 expression are associated with a higher DCR and longer PFS in patients with advanced PDAC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.