Ganglioside Monosialic Acid Alleviates Peripheral Neuropathy Induced by Utidelone Plus Capecitabine in Metastatic Breast Cancer From a Phase III Clinical Trial

Abstract

Purpose: This study aimed to assess the efficacy of utidelone, a novel genetically engineered epothilone analog, combined with capecitabine in our center and, furthermore, to identify whether ganglioside monosialic acid (GM1) improved chemotherapy-induced peripheral neurotoxicity (CIPN).

Methods: Fifty-five eligible female patients with metastatic breast cancer were enrolled in our single-center phase III BG01-1323L trial. Utidelone combined with capecitabine-induced peripheral neuropathy was analyzed, and susceptible genes were detected in a germline panel by next-generation sequencing (NGS).

Results: In our single-center study, median progression-free survival and overall survival (OS) improved in the utidelone plus capecitabine group (mPFS: 238 vs. 189 days, P = 0.263; OS: 20.9 vs. 12.9 months, P = 0.326). The median time to severe CIPN reported was 29 days in grade 1, 49 days in grade 2, and 103 days in grade 3. Greatly longer improvement time was indicated in grade 1 (77 vs. 20 days in grade 2, 13 days in grade 3). In the combined group, 19 patients with G2 or G3 CIPN were assigned to the GM1 group and 9 patients to the control group. After intervention, the GM1 group was reported to demonstrate a statistically lower incidence of grade 3 CIPN [GM1 group: 1 of 19 (5.3%); control group: 4 of 9 (44.4%), P = 0.026]. However, there were no statistically significant differences in germline single nucleotide polymorphism (SNP) between grade 3 and grade 1 CIPN cohorts.

Conclusion: Ganglioside monosialic acid potentially decreases severe utidelone plus capecitabine-induced peripheral neuropathy in metastatic breast cancer, and further investigation is needed to validate the manageable efficacy of GM1 in CIPN.

Clinical trial registration: ClinicalTrials.gov, identifier NCT02253459.

Keywords: Ganglioside monosialic acid; Utidelone; capecitabine; chemotherapy-induced peripheral neurotoxicity; metastatic breast cancer.

Copyright © 2020 Xu, Wang, Jiang, Cao, Jiang, Xu and Sun.

Figures

FIGURE 1

Patient disposition in our center population in the BG01-1323L study. Flow diagram showing patient enrollment, allocation, follow-up, and analysis in our center population from the BG01-1323L study.

FIGURE 2

IRC-assessed PFS (A) and OS (B) in our center population. CI, confidence interval; X capecitabine, ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; mo, months; U, utidelone; PFS, progression-free survival; PgR, progesterone receptor; IRC, independent radiology review committee; and OS, overall survival.

FIGURE 3

Bar chart of patient-reported chemotherapy-induced peripheral neuropathy in total population and our center population (A), the time of appearance, remission and duration of serious CIPN (B) bar chart of patient-reported grade 2 and grade 3 of CIPN in GM1 and control groups (C).

FIGURE 4

IRC-assessed PFS among patients with diverse grades of CIPN (A), IRC-assessed PFS between GM1 and control groups (B), IRC-assessed OS among patients with diverse grades of CIPN (C), IRC-assessed OS between GM1 and control groups (D).