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

Junnan Xu,Cui Jiang,Binghe Xu,Tao Sun,Hui Cao,Junhan Jiang,Yan Wang

doi:10.3389/fonc.2020.524223

Abstract

PurposeThis 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).MethodsFifty-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).ResultsIn 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.ConclusionGanglioside 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 RegistrationClinicalTrials.gov, identifier NCT02253459.

Highlights

Breast cancer accounted for 25% of all newly diagnosed cancer worldwide and 15% of all newly diagnosed cancer in females in China [1]
During the period from October 11, 2014, to October 15, 2015, a total of 55 female patients were randomized in our center populations: 39 to the utidelone plus capecitabine arm and 16 to the capecitabine-alone arm
By the data cutoff date for progression-free survival (PFS) and overall survival (OS) analysis (December 17, 2018), the median follow-up was 626 days in the utidelone plus capecitabine arm and 388 days in the capecitabinealone arm

Summary

Introduction

Breast cancer accounted for 25% of all newly diagnosed cancer worldwide and 15% of all newly diagnosed cancer in females in China [1]. Despite advances in target therapy, endocrine therapy, and immunotherapy, chemotherapy remains the fundamental strategy for breast cancer patients. The standard adjuvant chemotherapy significantly improved disease-free survival (DFS) and overall survival (OS) in patients with early breast cancer, especially anthracyclines and taxanes [2]. Above 30% of early breast cancer relapses or distant metastasis contributed to drug resistance in a metastatic setting, and this has led to an increase in heavy pretreatment with and resistance to anthracyclines and taxanes. Some metastatic breast cancer patients are limited to anthracyclines due to the risk of cumulative cardiac-related toxicities. Several novel chemotherapies have been approved for patients with metastatic breast cancer, including gemcitabine, capecitabine, and eribulin, especially for metastatic triple-negative breast cancer [3]

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