Oncotarget

Research Papers:

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

Yasutaka Tono, Mikiya Ishihara _, Yoshihiro Miyahara, Satoshi Tamaru, Hiroyasu Oda, Yoshiki Yamashita, Isao Tawara, Hiroaki Ikeda, Hiroshi Shiku, Toshiro Mizuno and Naoyuki Katayama

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Oncotarget. 2018; 9:14909-14921. https://doi.org/10.18632/oncotarget.24504

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Abstract

Yasutaka Tono1,2, Mikiya Ishihara2, Yoshihiro Miyahara3, Satoshi Tamaru2, Hiroyasu Oda2, Yoshiki Yamashita2, Isao Tawara1, Hiroaki Ikeda3,4, Hiroshi Shiku3, Toshiro Mizuno2 and Naoyuki Katayama1,2

1Department of Hematology and Oncology, Mie University Graduate School of Medicine, 514-8507 Mie, Japan

2Department of Medical Oncology, Mie University Hospital, 514-8507 Mie, Japan

3Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, 514-8507 Mie, Japan

4Department 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.


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