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Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer

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Abstract

Purpose

Dual anti-HER2 targeted therapy and chemotherapy is the current first-line standard of care for HER2 + metastatic breast cancer (MBC), with endocrine therapy (ET) the backbone of treatment in hormone receptor positive (HR +) disease. The potential ET benefit in HER2 + /HR + patients is unknown as pivotal dual anti-HER2 clinical trials precluded ET use.

Methods

Real-world data from a multi-site registry of consecutive HER2 + MBC patients treated at clinician discretion were examined. Patients that were HR + (ER + and/or PR +) and had received first-line chemotherapy alongside trastuzumab and pertuzumab were explored. Of 362 patients in the registry, 215 were excluded due to being HR- (n = 210) or not receiving chemotherapy (n = 5).

Results

Of the 147 patients included, 91 (62%) received concurrent ET and 56 (38%) had not. Comparing the groups, there were no significant differences in age, performance status, metastatic sites, use of previous therapy and de novo metastatic disease. More patients with ER + PR + disease versus those with ER + PR- or ER-PR + received ET (73 vs 45%). The addition of ET was associated with significantly improved 5-year PFS (HR 0.58, CI 0.37–0.89, p = 0.014) and OS (HR 0.52, CI 0.31–0.90, p = 0.018), with no increase in adverse events noted.

Conclusion

The addition of ET to first-line dual anti-HER2 therapy post chemotherapy in patients with HER2 + /HR + MBC was associated with major gains in PFS and OS with no safety concerns evident. Further studies of this combination are justified, along with studies of how best to integrate other agents that are active in this patient subset, including CDK4/6 inhibitors.

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Data availability

The dataset generated during and analysed during the current study are available from the corresponding author on reasonable request.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Division of Personalised Oncology, Walter and Eliza Hall, 1G Royal Pde, Parkville, VIC, 3052, Australia

    Matthew Loft, Sheau Wen Lok, Angelyn Anton, Vanessa Wong, Peter Gibbs & Lucy Gately

  2. Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia

    Matthew Loft, Peter Gibbs & Lucy Gately

  3. Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia

    Sheau Wen Lok & Richard De Boer

  4. Department of Medical Oncology, Canberra Hospital, Garran, ACT, Australia

    Laeeq Malik

  5. Department of Medical Oncology, Western Health, Footscray, VIC, Australia

    Sally Greenberg & Peter Gibbs

  6. Department of Medical Oncology, Austin Health, Heidelberg, VIC, Australia

    Belinda Yeo

  7. Department of Medical Oncology, Eastern Health, Box Hill, VIC, Australia

    Angelyn Anton

  8. Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia

    Angelyn Anton

  9. Department of Medical Oncology, Royal Brisbane Hospital, Herston, QLD, Australia

    Michelle Nottage

  10. Department of Medical Oncology, Ballarat Health, Ballarat, VIC, Australia

    Vanessa Wong

  11. Department of Medical Oncology, Royal Hobart Hospital, Hobart, TAS, Australia

    Louise Nott

  12. Department of Medical Oncology, South West Healthcare, Warrnambool, VIC, Australia

    Ian M. Collins

  13. Department of Medical Oncology, Goulburn Valley Health, Shepparton, VIC, Australia

    Javier Torres

  14. Department of Medical Oncology, Northern Hospital, Epping, VIC, Australia

    Frances Barnett

  15. Department of Medical Oncology, Newcastle Private Hospital, New Lambton Heights, NSW, Australia

    Janine M. Lombard

Authors
  1. Matthew Loft
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  2. Sheau Wen Lok
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  7. Angelyn Anton
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  8. Michelle Nottage
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  10. Louise Nott
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  11. Ian M. Collins
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  15. Peter Gibbs
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  16. Lucy Gately
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Contributions

ML, SWL, PG and LG: contributed to conceptualization, methodology and design. All authors contributed to material preparation and data collection. ML: analysis and the first draft was performed and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Matthew Loft.

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Conflict of interest

SWL has received institutional research grants from Novartis and royalty payments. RDB is on the advisory board for AstraZeneca, Novartis and Gilead, has received speaker honoraria from Gilead and Eli Lilly and research grants from Pfizer, Novartis and AstraZeneca. BY is on the advisory board for Roche/Genetech, and has received speaker honoraria and travel grant from Roche. AA has received institutional research funding from Bayer, AstraZeneca, Amgen, Astellas, Janssen, MSD and Mundipharma, and honoraria from Amgen, Janssen and Eisai. VW has received institutional research funding from Pierre Fabre, Amgen, Roche, MSD, AstraZeneca and Merck, and speaker honoraria from Amgen and Janssen. JM is on the advisory board for GSK and AstraZeneca and has received support for virtual education meeting attendance from GSK, AstraZeneca and Novartis. ML, LM, SG, MN, LN, IC, JT, FB, PG and LG have no conflicts of interest to disclose.

Ethical approval

This study received ethics approval for the collection and utilization of de-identified patient data from individual sites and from the ethics committee overseeing the TABITHA registry.

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Loft, M., Lok, S.W., De Boer, R. et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Breast Cancer Res Treat 198, 67–74 (2023). https://doi.org/10.1007/s10549-022-06856-1

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  • DOI: https://doi.org/10.1007/s10549-022-06856-1

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