High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin-but not with treatment of physician's choice-in the EMBRACE study

Yasuo Miyoshi, Yuta Yoshimura, Kenichi Saito, Kenzo Muramoto, Michiko Sugawara, Karenza Alexis, Kenichi Nomoto, Seigo Nakamura, Toshiaki Saeki, Junichiro Watanabe, Jose Manuel Perez-Garcia, Javier Cortes, Yasuo Miyoshi, Yuta Yoshimura, Kenichi Saito, Kenzo Muramoto, Michiko Sugawara, Karenza Alexis, Kenichi Nomoto, Seigo Nakamura, Toshiaki Saeki, Junichiro Watanabe, Jose Manuel Perez-Garcia, Javier Cortes

Abstract

Background: Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS).

Methods: The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively.

Results: Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin.

Discussion: This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures.

Trial registration: www.ClinicalTrials.gov code: NCT00388726.

Keywords: Absolute lymphocyte count; Eribulin; Metastatic breast cancer; Overall survival; Treatment of physician’s choice.

Conflict of interest statement

Y. Miyoshi: reports grants from Eisai, Chugai, MSD, Kyowa-Kirin, Eli Lilly, and Taiho; personal fees from Eisai, Chugai, AstraZeneca, Eli Lilly, and Pfizer. Y. Yoshimura: is an employee of Eisai Co., Ltd. K. Saito: is an employee of Eisai Inc. K. Muramoto: is an employee of Eisai Co., Ltd. M. Sugawara: is an employee of Eisai Co., Ltd. K. Alexis: is a former employee of Eisai Inc. K. Nomoto: is an employee of Eisai Inc. S. Nakamura: reports grants from Chugai, Daiichi Sankyo, Eisai, Kyowa-Kirin, Novartis, Pfizer, Taiho, and Takeda; personal fees from AstraZeneca, Bayer, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa-Kirin, Nippon Kayaku, Novartis, Pfizer, Taiho, and Takeda. T. Saeki: has received grants from AstraZeneca, Eisai, MSD, Ono Pharmaceutical, Kyowa-Kirin, Daiichi Sankyo, Sawai, Taiho, Chugai, Nihon Medi-Physics, Nippon Kayaku, Novartis, Hamamatsu Photonics, and Fuji Pharma; personal fees from AstraZeneca, Ono Pharmaceutical, Kyowa-Kirin, Taiho, Chugai, Novartis, and Fuji Pharma. J. Watanabe: reports personal fees from Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Novartis, and Pfizer. J.M. Perez-Garcia: reports an advisory role with Roche and Lilly. J. Cortes: reports consulting for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, and GSK; honoraria for Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, and Merck Sharp & Dohme; research funding to the institution for Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffman-La Roche, Guardant health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London, and Seagen; stock/patents/intellectual property of MedSIR.

Figures

Fig. 1
Fig. 1
Interaction between treatment and baseline ALC (P < 0.001). In patients with low ALC, the median OS was 11.6 and 10.3 months in the eribulin and TPC arms, respectively (HR 1.002; 95% CI 0.800–1.253; P = 0.989). ALC absolute lymphocyte count, CI confidence interval, HR hormone receptor, OS overall survival
Fig. 2
Fig. 2
Interaction between treatment and baseline NLR (P = 0.218). In patients with low NLR, the median OS was 15.9 and 12.6 months in the eribulin and TPC arms, respectively (HR 0.755; 95% CI 0.572–0.996; P = 0.046). CI confidence interval, OS overall survival
Fig. 3
Fig. 3
The forest plot for baseline ALC (ALC absolute lymphocyte count, CI confidence interval, ECOG Eastern Cooperative Oncology Group, ER oestrogen receptor, HER2 human epidermal growth factor receptor-2, HR hormone receptor, OS overall survival, PgR progesterone receptor. aDisease progression on or within 6 months of taxane treatment

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Source: PubMed

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