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A dynamic portrait of adverse events for breast cancer patients: results from a phase II clinical trial of eribulin in advanced HER2-negative breast cancer

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Abstract

Purpose

Adverse events (AE) during oncology clinical trials are typically reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), which provides information about the frequency and severity of AEs from the provider’s perspective. Instruments that track patient-reported outcomes (PRO) complement the CTCAE and provide additional patient-centered information about the toxicity profile of an anti-cancer drug.

Methods

We conducted a single-arm, open-label phase II study of eribulin as first- or second-line therapy for metastatic hormone receptor-positive/HER2-negative (HR+/HER2−) or triple-negative breast cancer (TNBC). Patients were recruited simultaneously into each cohort by tumor subtype. The primary endpoint was overall response rate (ORR). Secondary endpoints included evaluation of toxicity by CTCAE and PRO instruments and agreement between CTCAE and PRO. The study also investigated single-nucleotide polymorphisms (SNPs) associated with treatment-induced neurotoxicity.

Results

83 patients were enrolled: 45 into the HR+/HER2− cohort and 38 into the TNBC cohort. The ORR was 35.6% (90% CI 24–39%) in the HR+/HER2− cohort and 13.2% (90% CI 5–26%) in the TNBC cohort. Stable disease as the best response was recorded in 55.1% of patients with HR+/HER2− disease and 60.5% with TNBC. Toxicity analysis revealed a discordance between CTCAE and PRO assessment in many patients, with a focus on fatigue, alopecia, and neuropathy. Pharmacogenomic analysis identified SNPs associated with treatment-induced peripheral neuropathy.

Conclusions

Eribulin is active in HER2− breast cancer. This study reveals that provider-assessed AEs can vary greatly from patient experiences. Future studies should incorporate CTCAE and PRO instruments to improve reporting of treatment-related AEs.

ClinicalTrials.gov Registration: NCT01827787

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Timothy K. Erick, PhD, a full-time medical writer employed by Dana-Farber Cancer Institute, assisted in the editing and preparation of the final manuscript. Kaitlyn Bifolck, B.A., a full-time editor employed by Dana-Farber Cancer Institute, assisted in the editing, preparation, and submission of the final manuscript.

Funding

Supported in part by an investigator-initiated grant from Eisai, Inc.

Author information

Authors and Affiliations

  1. Dana-Farber Cancer Institute, Boston, MA, USA

    Otto Metzger Filho, Anita Giobbie-Hurder, Nancy U. Lin, Meredith Faggen, Michael Constantine, Jeanna Walsh, Rachel A. Freedman & Harold J. Burstein

  2. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Steven Come

  3. Eastern Maine Medical Center, Bangor, ME, USA

    Thomas Openshaw

  4. Simon Cancer Center at Indiana University, Indianapolis, IN, USA

    Bryan Schneider

  5. Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02468, USA

    Otto Metzger Filho

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Contributions

OMF: conceptualization, data curation, formal analysis, investigation, methodology, resources, validation, writing—original draft, and writing—review and editing. AG-H: conceptualization, data curation, formal analysis, investigation, methodology, resources, software, writing—original draft, and writing—review and editing. NUL: data curation, investigation, writing—review and editing. MF: data curation, investigation, writing—review and editing. SC: data curation, investigation, writing—review and editing. TO: data curation, investigation, writing—review and editing. MC: data curation, investigation, writing—review and editing. JW: data curation, investigation, writing—review and editing. RF: data curation, investigation, writing—review and editing. BS: data curation, formal analysis, investigation, methodology, software, writing—review and editing. HJB: conceptualization, data curation, investigation, writing—original draft, and writing—review and editing. ELM: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, validation, writing—original draft, and writing—review and editing.

Corresponding author

Correspondence to Otto Metzger Filho.

Ethics declarations

Conflict of interest

O. Metzger Filho reports research funding to institution from Abbvie, Cascadian Therapeutics, Eisai, Pfizer, Roche/Genentech, and Susan G. Komen for the Cure; consulting/advisory roles for Abbvie, G1 Therapeutics, and Groupo Oncoclinicas (Brazil); and honoraria from Roche (Brazil); travel/accommodations/expenses from Grupo Oncoclinicas. N.U. Lin reports research funding to institution from Seattle Genetics, Genentech, Pfizer, Merck; advisory board roles for Daichii Sankyo, Puma, Seattle Genetics; and royalties from UpToDate. R. Freedman reports research funding to institution from Eisai and Puma. E.L. Mayer reports research funding to institution from Pfizer, Eisai. Advisory Board: Lilly, Novartis, and Eisai. All other authors report no disclosures.

Ethical approval

This trial was approved by the individual institutional review boards at participating cancer centers and conducted according to the provisions of the Declaration of Helsinki and Good Clinical Practice.

Informed consent

Informed consent was obtained from all individual participants included in the study. All patients provided written informed consent before any study-related procedures.

Research involving human participants

This trial was approved by the individual institutional review boards at participating cancer centers and conducted according to the provisions of the Declaration of Helsinki and Good Clinical Practice.

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Filho, O.M., Giobbie-Hurder, A., Lin, N.U. et al. A dynamic portrait of adverse events for breast cancer patients: results from a phase II clinical trial of eribulin in advanced HER2-negative breast cancer. Breast Cancer Res Treat 185, 135–144 (2021). https://doi.org/10.1007/s10549-020-05928-4

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