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

• Published in: Breast cancer research and treatment Vol. 205; no. 1; pp. 87 - 95
• Main Authors: Verschoor, Noortje, Bos, Manouk K., de Kruijff, Ingeborg E., Van, Mai N., Kraan, Jaco, Drooger, Jan C., Zuetenhorst, Johanna M., Wilting, Saskia M., Sleijfer, Stefan, Jager, Agnes, Martens, John W. M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2024; Springer Nature B.V
• Subjects: Breast cancer; Cancer therapies; Chemotherapy; Clinical Trial; ErbB-2 protein; Medicine; Medicine & Public Health; Metastases; Metastasis; Oncology; Patients; Taxanes; Trastuzumab; Tumor cells; Tumors; Metastatic breast cancer; Circulating tumor cells; HER2; Trastuzumab; Predictive biomarker
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-023-07231-4

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.