Gemcitabine–Paclitaxel Chemotherapy for Patients with Advanced Urothelial Cancer Refractory to Cisplatin-Based Chemotherapy: Predictive Role of PGK1 for Treatment Response to Cytotoxic Chemotherapy

Abstract

An investigation of alternatives to immune checkpoint inhibitors for advanced urothelial cancer (aUC), with biologic information, is urgently needed. Clinical data for 53 patients who received gemcitabine–paclitaxel therapy (GP) as 2nd-line chemotherapy for aUC refractory to platinum-based chemotherapy were retrospectively reviewed. The efficacy and tolerability of GP were evaluated, and the predictive value of phosphoglycerate kinase 1 (PGK1) immunostained in surgical specimens was investigated for treatment outcomes in 1st- and 2nd-line chemotherapy. GP was associated with an objective response rate of 35.8% and a median overall survival duration of 12.3 months. Multivariate analysis showed that PS2 and 1st- and 2nd-line non-response are independent predictors of worse progression-free survival and that PS2 and 1st-line non-response are independent predictors of worse overall survival. Adverse events were manageable, and no therapy-related deaths occurred. Non-response rates to 1st-line chemotherapy were significantly higher in patients with a high expression of PGK1 in the nucleus than in those with low expression (p = 0.006). Our study demonstrates the efficacy and tolerability of 2nd-line GP for patients with aUC who are refractory to platinum-based chemotherapy. Moreover, PGK1 in the nucleus was predictive values for resistance to platinum-based chemotherapy in aUC.

Gemcitabine/nab‐paclitaxel vs gemcitabine/carboplatin for advanced urothelial carcinoma

“…Taxanes have demonstrated modest efficacy in mUC treatment [11,12]. The combination of either paclitaxel or docetaxel with gemcitabine (GT) has shown promising efficacy and tolerance in second-line of platinum-refractory setting [13,14], or as a first-line treatment [15][16][17][18]. However, all the studies on taxanes were retrospective or small-sized prospective studies; no randomised trial has directly compared GT with platinum-based chemotherapy.…”

Biomarkers for Early Detection of Cancer: Molecular Aspects

“…In this regard, in the paper by Koguchi et al [ 6 ] the predictive value of phosphoglycerate kinase 1 (PGK1) was investigated for treatment outcomes in first- and second-line chemotherapy in patients with advanced urothelial cancer. It was observed that the non-response rates to first-line chemotherapy were significantly higher in patients with a high expression of PGK1 in the nucleus than in those with a low expression.…”