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. 2024 Jan 17;24(1):91.
doi: 10.1186/s12885-024-11851-4.

Neoadjuvant trastuzumab deruxtecan (T-DXd) with response-directed definitive therapy in early stage HER2-positive breast cancer: a phase II study protocol (SHAMROCK study)

Gavin P Dowling  1   2 , Sinead Toomey  3 , Philip Bredin  3   4 , Imelda Parker  5 , Eibhlin Mulroe  5 , Jacinta Marron  5 , Olivia McLoughlin  5 , Ausra Teiserskiene  5 , Colm Power  3   4 , Anne Marie O'Shea  4 , Megan Greally  4 , Patrick G Morris  3   4 , Deirdre Duke  3   4 , Arnold D K Hill  3   4 , Bryan T Hennessy  3   4
Affiliations

Neoadjuvant trastuzumab deruxtecan (T-DXd) with response-directed definitive therapy in early stage HER2-positive breast cancer: a phase II study protocol (SHAMROCK study)

Gavin P Dowling et al. BMC Cancer. .

Abstract

Background: The current standard of care in the neoadjuvant setting for high-risk HER2-positive (HER2 +) breast cancer is to combine systemic chemotherapy with dual HER2 blockade, trastuzumab and pertuzumab. Targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer. To improve treatment-associated toxicity, chemotherapy-sparing approaches are currently being investigated. Trastuzumab deruxtecan (T-DXd) is an HER2-directed antibody-drug-conjugate (ADC) with promising results in the metastatic setting for HER2-positive breast cancer. The SHAMROCK study investigates neoadjuvant T-DXd in early stage HER2-positive breast cancer, using pathological complete response (pCR) rate as the primary endpoint.

Methods: This is a phase II open-label, single arm, adaptive multi-centre trial of T-DXd in the neoadjuvant setting in stage 2-3 HER2-positive breast cancer. Eligible patients will receive 5.4 mg/kg of T-DXd intravenously every 3 weeks for up to 6 cycles. A repeat biopsy will performed after 2 cycles for the RNA disruption index (RDI) score assessment. According to their likelihood of pCR, as determined by the RDI score, patients will either undergo 4 or 6 cycles of T-DXd prior to imaging. Patients with imaging complete response (iCR) after either 4 or 6 cycles will proceed to surgery. Patients who do not achieve iCR will either undergo further systemic therapy or proceed to surgery.

Discussion: The SHAMROCK study is a chemotherapy-sparing approach to curative intent treatment, investigating neoadjuvant T-DXd. We hypothesise that neoadjuvant T-DXd will have a high pCR rate and be associated low toxicity in early stage HER2-positive breast cancer.

Trial registration: EudraCT Number: 2022-002485-32; ClinicalTrials.gov identifier: NCT05710666; Cancer Trials Ireland study number: CTRIAL-IE 22-01.

Keywords: Breast cancer; HER2-positive; Neoadjuvant; Pathological Complete Response; Trastuzumab deruxtecan.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study Schema of SHAMROCK study. Abbreviations: RDI RNA disruption index, T-DXd trastuzumab deruxtecan, iCR imaging complete response
See this image and copyright information in PMC

References

    1. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25–32. doi: 10.1016/S1470-2045(11)70336-9. - DOI - PubMed
    1. Dowling GP, Keelan S, Toomey S, Daly GR, Hennessy BT, Hill ADK. Review of the status of neoadjuvant therapy in HER2-positive breast cancer. Front Oncol. 2023;13:1066007. doi: 10.3389/fonc.2023.1066007. - DOI - PMC - PubMed
    1. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–172. doi: 10.1016/S0140-6736(13)62422-8. - DOI - PubMed
    1. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617–628. doi: 10.1056/NEJMoa1814017. - DOI - PubMed
    1. Hurvitz SA, Martin M, Jung KH, Huang CS, Harbeck N, Valero V, et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019;37(25):2206–2216. doi: 10.1200/JCO.19.00882. - DOI - PMC - PubMed

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