Influence of LGALS3 polymorphisms on chemotherapy-induced peripheral neuropathy in patients with metastatic pancreatic cancer treated with gemcitabine and nab-paclitaxel: an exploratory biomarker analysis of the GENESECT study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting factor and determinant of treatment continuation in patients receiving anticancer drugs. CIPN often persists even after treatment discontinuation and negatively impacts patients' quality of life. At present, the risk factors for CIPN development remain unclear. This study aimed to exploratively examine the association between genetic polymorphisms and CIPN in Japanese patients with metastatic pancreatic cancer treated with gemcitabine and nab-paclitaxel (GnP) as first-line chemotherapy. This exploratory analysis of the GENESECT dataset included 65 patients with metastatic pancreatic cancer who received GnP therapy. The association of 14 genetic polymorphisms with CIPN was analyzed by multivariate Firth logistic regression with Benjamini-Hochberg correction for multiple comparisons. The Kaplan-Meier curves among genetic polymorphisms were analyzed using log-rank test to compare the cumulative dosage of nab-paclitaxel until CIPN ≥ grade 2. Results were considered significant at p < 0.05. The AA and AC variants of LGALS3 rs4652 tended to be associated with CIPN ≥ grade 2 (adjusted odds ratio (OR), 0.248; 95% confidence interval (CI), 0.055-1.02, p = 0.053), and a cumulative dose of nab-paclitaxel ≥ 1625 mg/m2 (median) was significantly associated (adjusted OR, 6.72; 95% CI, 2.02-27.0, p = 0.002). Patients with AA and AC variants of LGALS3 rs4652 tended to have larger median cumulative dosages of nab-paclitaxel until the development of CIPN ≥ grade 2 (4050 mg/m2 vs. 1600 mg/m2, p = 0.073). LGALS3 rs4652 may represent a promising candidate biomarker that requires prospective validation.