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Impact of prior (neo)adjuvant trastuzumab (NAT) exposure on the efficacy of HER2-targeted therapy for metastatic breast cancer

Abstract

Purpose

Trastuzumab, pertuzumab, and docetaxel are the standard first-line therapy for HER2-positive (HER2+) metastatic breast cancer (MBC). However, only 10% of patients received neoadjuvant and/or adjuvant trastuzumab (NAT) in the registration trial (NCT00567190). In contemporary practice, the majority of recurrent HER2+ MBC patients had prior NAT. We explore any impact of prior therapy on the efficacy of dual HER2-targeted antibody with taxane therapy for metastatic disease.

Methods

Utilising a prospective national registry, clinico-pathological, treatment, and outcome data for HER2+ MBC patients diagnosed between October 2006 and January 2019 were collected. Survival was estimated by the Kaplan–Meier method and compared among groups by log-rank test.

Results

Of 287 HER2+ MBC patients, 222 (77%) received first-line trastuzumab, pertuzumab, and taxane therapy. There were 130 (45%) with de novo MBC. Of the recurrent MBC patients 107/157 (68%) had received NAT. The median progression-free survival (PFS) among patients who received NAT was 15.8 months compared with 24.3 months without prior NAT (hazard ratio [HR] 1.45, 95% CI 1.05–2.03, p = 0.03). The median overall survival (OS) was 42.7 months in patients who had NAT, and was not reached in those who did not (HR 1.80, 95% CI 1.12–2.90, p = 0.02). However, when excluding de novo MBC patients, prior NAT exposure was no longer significantly associated with survival (p = 0.11). De novo MBC patients had the longest median PFS (25.2 months) and OS (91.2 months).

Conclusions

Prior receipt of NAT was associated with inferior median PFS following first-line HER2-based therapy in the metastatic setting. However, prior NAT exposure did not significantly impact OS, supporting the efficacy of taxane, trastuzumab, pertuzumab combination for first-line HER2+ MBC regardless of prior NAT exposure. Patients with de novo MBC had the longest survival, suggesting stratification for synchronous versus metachronous disease in prospective clinical trials of MBC should be considered.

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Funding

The TABITHA registry is sponsored by BioGrid Australia and has received financial support from Roche Products Pty Limited.

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Authors and Affiliations

Authors

Contributions

Yada Kanjanapan contributed to the study conception and design. Material preparation and data collection was performed by Julie Johns, Michael Harrold and Yada Kanjanapan. Data analysis was performed by Yada Kanjanapan, with input in data interpretation by Sheau Wen Lok, Peter Gibbs, Richard De Boer, Belinda Yeo, Sally Greenberg, Frances Barnett, Louise Nott, Gary Richardson, Rachel Wong, Michelle Nottage, Ian M Collins, Javier Torres, Janine Lombard and Laeeq Malik. The first draft of the manuscript was written by Yada Kanjanapan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yada Kanjanapan.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study has been approved by the institutional research ethics committee in all the participating sites.

Informed consent

A waiver for informed consent was granted by the institutional research ethics committee for this retrospective study in all the participating sites.

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Kanjanapan, Y., Lok, S.W., Gibbs, P. et al. Impact of prior (neo)adjuvant trastuzumab (NAT) exposure on the efficacy of HER2-targeted therapy for metastatic breast cancer. Breast Cancer Res Treat 184, 87–95 (2020). https://doi.org/10.1007/s10549-020-05825-w

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  • DOI: https://doi.org/10.1007/s10549-020-05825-w

Keywords

  • Trastuzumab
  • Pertuzumab
  • Metastatic breast cancer
  • De novo