TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis
Background: The docetaxel (T), carboplatin (C) and trastuzumab (H) regimen has been used in the (neo-) adjuvant treatment of HER2+ early stage breast cancer (ESBC). Lapatinib (L) a small molecule HER2 antagonist produces clinical responses following H failure. Methods: We randomly assigned 88 patie...
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Medical Journals Sweden
2025-06-01
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| Series: | Acta Oncologica |
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| Online Access: | https://medicaljournalssweden.se/actaoncologica/article/view/43143 |
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| author | John Crown Alex J. Eustace Denis M. Collins Maccon Keane Linda Coate John Kennedy Seamus O'Reilly Catherine Kelly Miriam O'Connor Michael Martin Conleth Murphy Karen Duffy Janice Walshe Giuseppe Gullo Thamir Mahgoub Alberto Alvarez-Iglesias Imelda Parker Vicky Donachie Ausra Teiserskiene Stephen F. Madden Brian Moulton Norma O'Donovan Bryan T. Hennessy |
| author_facet | John Crown Alex J. Eustace Denis M. Collins Maccon Keane Linda Coate John Kennedy Seamus O'Reilly Catherine Kelly Miriam O'Connor Michael Martin Conleth Murphy Karen Duffy Janice Walshe Giuseppe Gullo Thamir Mahgoub Alberto Alvarez-Iglesias Imelda Parker Vicky Donachie Ausra Teiserskiene Stephen F. Madden Brian Moulton Norma O'Donovan Bryan T. Hennessy |
| author_sort | John Crown |
| collection | DOAJ |
| description | Background: The docetaxel (T), carboplatin (C) and trastuzumab (H) regimen has been used in the (neo-) adjuvant treatment of HER2+ early stage breast cancer (ESBC). Lapatinib (L) a small molecule HER2 antagonist produces clinical responses following H failure.
Methods: We randomly assigned 88 patients with stages Ic–III HER2+ESBC to receive neoadjuvant TCH, TCL or TCHL followed by surgery and 1 year of H. The primary endpoint was pathological complete response (pCR). Secondary objectives were overall and disease-free survival (OS, DFS).
Results: The TCL arm was closed following demonstration of inferiority of L in another trial. The pCR rates for TCH and TCHL were 52.8 and 51.6 (p = 1.0). At a median 4.8 years follow-up, TCHL patients had a significantly superior DFS; however, OS was similar. Prophylactic loperamide reduced the frequency of diarrhoea. Serum biomarker analysis identified a link between high tumour T-cell levels and high red blood cell, haematocrit, and haemoglobin following commencement of therapy.
Interpretation: The study did not meet its primary endpoint of superior pCR. TCHL produced a significant improvement in DFS. Our study and others suggest a possible role for L in neoadjuvant therapy of HER2+ ESBC.
Clinical Trial Registration: NCT01485926.
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| format | Article |
| id | doaj-art-401dc3ce9aaf4929ade95c8534b974f9 |
| institution | OA Journals |
| issn | 1651-226X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Oncologica |
| spelling | doaj-art-401dc3ce9aaf4929ade95c8534b974f92025-08-20T02:03:23ZengMedical Journals SwedenActa Oncologica1651-226X2025-06-016410.2340/1651-226X.2025.43143TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysisJohn Crown0Alex J. Eustace1https://orcid.org/0000-0002-4092-1360Denis M. Collins2Maccon Keane3Linda Coate4John Kennedy5Seamus O'Reilly6Catherine Kelly7Miriam O'Connor8Michael Martin9Conleth Murphy10Karen Duffy11Janice Walshe12Giuseppe Gullo13Thamir Mahgoub14Alberto Alvarez-Iglesias15Imelda Parker16Vicky Donachie17Ausra Teiserskiene18Stephen F. Madden19Brian Moulton20Norma O'Donovan21Bryan T. Hennessy22Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland; Life Sciences Institute, Dublin City University, Dublin, IrelandLife Sciences Institute, Dublin City University, Dublin, Ireland; School of Biotechnology, Dublin City University, Glasnevin, Dublin, IrelandSchool of Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland; Cancer Biotherapeutics Research Group, School of Biotechnology, Dublin City University, Dublin, IrelandDepartment of Medical Oncology, Galway University Hospital, IrelandDepartment of Medical Oncology, University Hospital Limerick, IrelandDepartment of Medical Oncology, St James’s Hospital, Dublin, IrelandDepartment of Medical Oncology, Cork University Hospital, IrelandDepartment of Medical Oncology, Mater Hospital, Dublin, IrelandDepartment of Medical Oncology, Waterford Regional Hospital, IrelandDepartment of Medical Oncology, Sligo University Hospital, IrelandDepartment of Medical Oncology, Bons Secours Hospital, Cork, IrelandDepartment of Medical Oncology, Letterkenny University Hospital, Donegal, IrelandDepartment of Medical Oncology, St Vincent’s University Hospital, Dublin, IrelandDepartment of Medical Oncology, St Vincent’s University Hospital, Dublin, IrelandDepartment of Medical Oncology, University Hospital Limerick, IrelandHRB- Clinical Research Facility, Galway, IrelandCancer Trials Ireland/ICORG, Dublin, IrelandCancer Trials Ireland/ICORG, Dublin, IrelandCancer Trials Ireland/ICORG, Dublin, IrelandData Science Centre, Royal College of Surgeons in Ireland, Dublin, IrelandClinical Oncology Development Europe, Dublin, IrelandSchool of Biotechnology, Dublin City University, Glasnevin, Dublin, IrelandDepartment of Medical Oncology/ICORG/Cancer Trials Ireland, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, IrelandBackground: The docetaxel (T), carboplatin (C) and trastuzumab (H) regimen has been used in the (neo-) adjuvant treatment of HER2+ early stage breast cancer (ESBC). Lapatinib (L) a small molecule HER2 antagonist produces clinical responses following H failure. Methods: We randomly assigned 88 patients with stages Ic–III HER2+ESBC to receive neoadjuvant TCH, TCL or TCHL followed by surgery and 1 year of H. The primary endpoint was pathological complete response (pCR). Secondary objectives were overall and disease-free survival (OS, DFS). Results: The TCL arm was closed following demonstration of inferiority of L in another trial. The pCR rates for TCH and TCHL were 52.8 and 51.6 (p = 1.0). At a median 4.8 years follow-up, TCHL patients had a significantly superior DFS; however, OS was similar. Prophylactic loperamide reduced the frequency of diarrhoea. Serum biomarker analysis identified a link between high tumour T-cell levels and high red blood cell, haematocrit, and haemoglobin following commencement of therapy. Interpretation: The study did not meet its primary endpoint of superior pCR. TCHL produced a significant improvement in DFS. Our study and others suggest a possible role for L in neoadjuvant therapy of HER2+ ESBC. Clinical Trial Registration: NCT01485926. https://medicaljournalssweden.se/actaoncologica/article/view/43143HER2-positive breast cancerneoadjuvant therapyTrastuzumablapatinibtyrosine kinase inhibitors |
| spellingShingle | John Crown Alex J. Eustace Denis M. Collins Maccon Keane Linda Coate John Kennedy Seamus O'Reilly Catherine Kelly Miriam O'Connor Michael Martin Conleth Murphy Karen Duffy Janice Walshe Giuseppe Gullo Thamir Mahgoub Alberto Alvarez-Iglesias Imelda Parker Vicky Donachie Ausra Teiserskiene Stephen F. Madden Brian Moulton Norma O'Donovan Bryan T. Hennessy TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis Acta Oncologica HER2-positive breast cancer neoadjuvant therapy Trastuzumab lapatinib tyrosine kinase inhibitors |
| title | TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis |
| title_full | TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis |
| title_fullStr | TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis |
| title_full_unstemmed | TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis |
| title_short | TCHL – a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, rastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis |
| title_sort | tchl a phase ii neo adjuvant study assessing tch docetaxel carboplatin and trastuzumab and tchl docetaxel carboplatin rastuzumab and lapatinib in her 2 positive breast cancer patients a 5 year follow up with serum biomarker analysis |
| topic | HER2-positive breast cancer neoadjuvant therapy Trastuzumab lapatinib tyrosine kinase inhibitors |
| url | https://medicaljournalssweden.se/actaoncologica/article/view/43143 |
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