The following summary is “hENT1 Expression Predicts Response to Gemcitabine and Nab-Paclitaxel in Advanced Pancreatic Ductal Adenocarcinoma” published in the December 2022 issue of Oncology by Perera An et al.
Patients with advanced pancreatic ductal adenocarcinoma often get 1 of 2 first-line treatments: modified FOLFIRINOX (mFFX) or gemcitabine/nab-paclitaxel (GnP) advanced pancreatic ductal adenocarcinoma (PDAC). Contradictory evidence supports the hypothesis that human equilibrative nucleoslowide transporter 1 (hENT1) is a biomarker of gemcitabine in the adjuvant environment. In this work, researchers investigate hENT1 mRNA expression as a potential biomarker in PDAC with advanced stages. Patients with PDAC at an advanced stage participated in the COMPASS trial, which was an observational study with a prospective design.
The treating physician decided that a biopsy was necessary before starting chemotherapy. Whole genome and RNA sequencing followed laser capture microdissection of biopsy specimens. The maximum 2 statistics were used to establish the minimal detectable levels of hENT1 expression. A total of 253 individuals were included in the statistical examinations, with a median follow-up of 32 months; 138 received mFFX, and 92 received GnP. Median overall survival (OS) was longer for hENT1high than for hENT1low in the intent-to-treat sample, at 10.0 months versus 7.9 months, respectively (P=0.02).
The median overall survival for patients treated with mFFX (10.6 vs. 10.5 months, P=0.45) and the overall response rate (ORR; 35% vs. 28%, P=0.56) was not significantly different. ORR was higher in hENT1high tumors (43%) than in hENT1low tumors (21%; P=0.038) in patients treated with GnP. In this GnP-treated group, those with high hENT1high had a longer median OS than those with hENT1(P<0.001). Treatment response to GnP was predicted by hENT1low (interaction P=0.002). Gene expression profiling using hENT1 mRNA expression in advanced PDAC predicts the overall response rate survival in patients treated with GnP.