Pertuzumab, trastuzumab and eribulin mesylate therapy for previously treated advanced HER2-positive breast cancer: a feasibility study with analysis of biomarkers

// Yasutaka Tono 1, 2 , Mikiya Ishihara 2 , Yoshihiro Miyahara 3 , Satoshi Tamaru 2 , Hiroyasu Oda 2 , Yoshiki Yamashita 2 , Isao Tawara 1 , Hiroaki Ikeda 3, 4 , Hiroshi Shiku 3 , Toshiro Mizuno 2 and Naoyuki Katayama 1, 2 1 Department of Hematology and Oncology, Mie University Graduate School of Medicine, 514-8507 Mie, Japan 2 Department of Medical Oncology, Mie University Hospital, 514-8507 Mie, Japan 3 Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, 514-8507 Mie, Japan 4 Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, 852-8523 Nagasaki, Japan Correspondence to: Mikiya Ishihara, email: mishihara@clin.medic.mie-u.ac.jp Keywords: breast cancer; eribulin mesylate; HER2-positive; trastuzumab; pertuzumab Received: May 09, 2017      Accepted: February 07, 2018      Epub: February 16, 2018      Published: March 13, 2018 ABSTRACT The standard treatment for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is the triple combination of pertuzumab, trastuzumab and docetaxel, but some patients cannot tolerate taxane. To explore a non-taxane triple therapy, we conducted a feasibility study of pertuzumab, trastuzumab and eribulin mesylate (PTE) therapy for previously treated advanced HER2-positive breast cancer with analyses of quality of life and biomarkers. Ten patients were enrolled, two of whom had a history of docetaxel allergy. The median number of prior regimens was 3. The most common Grade 3 toxicities were leukopenia (70%) and neutropenia (70%). Grade 4 or 5 adverse events were not observed. An improving trend for the Functional Assessment of Cancer Therapy-Breast (FACT-B) score at 3 months was observed. Eight cases were included in the biomarker analysis. The peripheral CD8+ T cell/ CD4+Foxp3+ regulatory T cells (Tregs) ratio was significantly increased ( p = 0.039). The frequency of peripheral Tregs was associated with the trastuzumab trough concentration ( p = 0.019). In a non-clinical analysis, Eribulin mesylate significantly inhibited Ser473 Akt phosphorylation in PIK3CA wild-type cells and mutated cells. These results suggest that PTE therapy is a feasible and promising option for advanced HER2-positive breast cancer. Further investigation is warranted.