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- Title
Neoadjuvant trastuzumab deruxtecan (T-DXd) with response-directed definitive therapy in early stage HER2-positive breast cancer: a phase II study protocol (SHAMROCK study).
- Authors
Dowling, Gavin P.; Toomey, Sinead; Bredin, Philip; Parker, Imelda; Mulroe, Eibhlin; Marron, Jacinta; McLoughlin, Olivia; Teiserskiene, Ausra; Power, Colm; O'Shea, Anne Marie; Greally, Megan; Morris, Patrick G.; Duke, Deirdre; Hill, Arnold D. K.; Hennessy, Bryan T.
- 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.
- Subjects
HER2 positive breast cancer; TRASTUZUMAB; TUMOR classification; CANCER chemotherapy; CLOVER; RESEARCH protocols
- Publication
BMC Cancer, 2024, Vol 24, Issue 1, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/s12885-024-11851-4