Trastuzumab and First-line Taxane Chemotherapy in Metastatic Breast Cancer Patients with a HER2-negative Tumor and HER2-positive Circulating Tumor Cells: a Phase II Trial

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2024 Jan 30

PMID 38291268

Authors

Noortje Verschoor

Manouk K Bos

Ingeborg E de Kruijff

Mai N Van

Jaco Kraan

Jan C Drooger

Johanna M Zuetenhorst

Saskia M Wilting

Stefan Sleijfer

Agnes Jager

John W M Martens

Affiliations

Soon will be listed here.

Abstract

Purpose: HER2 overexpressing circulating tumor cells (CTCs) are observed in up to 25% of HER2-negative metastatic breast cancer patients. Since targeted anti-HER2 therapy has drastically improved clinical outcomes of patients with HER2-positive breast cancer, we hypothesized that patients with HER2 overexpressing CTCs might benefit from the addition of trastuzumab to chemotherapy.

Methods: In this single-arm, phase II trial, patients with HER2-positive CTCs received trastuzumab as addition to first-line treatment with taxane chemotherapy. Patients with detectable CTCs but without HER2 overexpression that received taxane chemotherapy only, were used as control group. The primary outcome measure was progression-free rate at 6 months (PFR6), with a target of 80%. In November 2022, the study was terminated early due to slow patient accrual.

Results: 63 patients were screened, of which eight patients had HER2-positive CTCs and were treated with trastuzumab. The median number of CTCs was 15 per 7.5 ml of blood (range 1-131) in patients with HER2-positive CTCs, compared to median 5 (range 1-1047) in the control group. PFR6 was 50% in the trastuzumab group and 54% in the taxane monotherapy group, with no significant difference in median PFS (8 versus 9 months, p = 0.51).

Conclusion: No clinical benefit of trastuzumab was observed, although this study was performed in a limited number of patients. Additionally, we observed a strong correlation between the number of evaluable CTCs and the presence of HER2-positive CTCs. We argue that randomized studies investigating agents that are proven to be solely effective in the HER2-positive patient group in patients with HER2-positive CTCs and HER2-negative tissue are currently infeasible. Several factors contribute to this impracticality, including the need for more stringent thresholds, and the rapidly evolving landscape of cancer treatments.

Citing Articles

Concordance of HER2 status between primary tumor and circulating tumor cells in breast cancer.

Xie P, Zhang X, Liu T, Song Y, Zhang Q, Wan D Discov Oncol. 2024; 15(1):760.

PMID: 39692928 PMC: 11655891. DOI: 10.1007/s12672-024-01663-0.

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