Abstract P2-15-10: Utidelone plus capecitabine versus capecitabine for heavily pretreated metastatic breast cancer and CIPN: Analysis of a single centre cohort
Authors: Xu Junnnan , Sun Tao 
Published: March 2020

Abstract
Objective In BG01-1323L trial, Utidelone, a novel genetically engineered epothilone analogue, plus capecitabine showed improved progression-free survival and overall survival in heavily pretreated metastatic breast cancer prior to anthracycline and taxane. Chemotherapy-induced peripheral neurotoxicity (CIPN) is the most common dose-limiting toxicity of utidelone plus capecitabine. The most samples were provided and CIPN related germline mutations were analyzed in our single centre. Recent study indicated ganglioside-monosialic acid (GM1) could decrease the incidence and severity of taxane-induced peripheral neuropathy. The aims of this study were to assess the efficacy of utidelone plus capecitabine in our centre and predictive role of mutations for CIPN, further to identify whether GM1 or Trivitamin B (IIIvB) improved CIPN.
Methods Fifty-four eligible female patients with metastatic breast cancer refractory to anthracycline and taxane were enrolled in our single centre in Phase 3 BG01-1323L trial. We randomly assigned to 39 cases in utidelone plus capecitabine and 16 cases in capecitabine alone until disease progression or unacceptable toxicity occurred. Progression-free survival and overall survival were assessed in our centre with the Kaplan-Meier product-limit method and Safety including neurotoxicity was both assessed in all participants and in our single centre. SNP were detected in germline panel including ABCB1, CDA, CYP19A1, CYP 2D6, DPYD, ERCC1, GSTP1, NQO1, TP53, TYMS and UGT1A1 and 363-genes panel was detected by NGS only in our centre.
Results In our single centre, median progression-free survival in the utidelone plus capecitabine group was 139 days compared with 137 days in the capecitabine alone group, p=0.642. Median overall survival improved in combined therapy (626 days vs 409 days, p=0.026). Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group. Compared with the ITT group, more grade1/2 CIPN (87.2% [34/39] in our centre vs 59% [89/270] in ITT) but less grade 3 (12.8% [5/39] in our centre vs 22% [92/270] in ITT) occurred in our single centre cohort. The potential reason for this difference of CIPN G3 was the palliative treatment target CIPN with GM1 or IIIvB in our single centre. Our analysis revealed that median time and duration of UIPN G3 was 10.29 weeks and 3.12 weeks in ITT and 15.67 weeks and 0.86 weeks in our single centre. Treatment with GM1 or IIIvB was associated with delay the median of CIPN G3 (10.29 weeks vs. 15.67 weeks) and reduction of the duration time (3.12 weeks vs. 0.86 weeks) in our centre compared to the ITT cohort. A tendency to extend the time of CIPN I/II was observed between GM1 and IIIvB groups (Grade I: 95.13 days vs 87.57 days, Grade II: 69.09 days vs 48.51 days). No associated germline SNP was found in Grade 3 CIPN and AXIN2, ATM and SMARCA4 mutation was associated with increased incidence CIPN by 363-gene panel.
Conclusion Utidelone plus capecitabine was more efficacious compared with capecitabine alone for progression-free survival with mild toxicity except for CIPN, less grade 3 CIPN was assessed in our single centre with GM1 and IIIvB, further investigation need to validate manageable efficacy of GM1 or IIIvB in CIPN in patients with utidelone plus capecitabine, as an effective option for patients with metastatic breast cancer.
Citation Format: Junnnan Xu, Tao Sun. Utidelone plus capecitabine versus capecitabine for heavily pretreated metastatic breast cancer and CIPN: Analysis of a single centre cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-10.