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
{"title":"TCHL -一项评估HER-2阳性乳腺癌患者TCH（多西紫杉醇、卡铂和曲妥珠单抗）和TCHL（多西紫杉醇、卡铂、拉妥珠单抗和拉帕替尼）的II期新辅助研究：5年随访血清生物标志物分析。","authors":"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","doi":"10.2340/1651-226X.2025.43143","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Interpretation: </strong>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.</p><p><strong>Clinical trial registration: </strong>NCT01485926.</p>","PeriodicalId":7110,"journal":{"name":"Acta Oncologica","volume":"64 ","pages":"751-760"},"PeriodicalIF":2.7000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171739/pdf/","citationCount":"0","resultStr":"{\"title\":\"TCHL - a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, trastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis.\",\"authors\":\"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\",\"doi\":\"10.2340/1651-226X.2025.43143\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Interpretation: </strong>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.</p><p><strong>Clinical trial registration: </strong>NCT01485926.</p>\",\"PeriodicalId\":7110,\"journal\":{\"name\":\"Acta Oncologica\",\"volume\":\"64 \",\"pages\":\"751-760\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171739/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Oncologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2340/1651-226X.2025.43143\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Oncologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2340/1651-226X.2025.43143","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
TCHL - a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, trastuzumab 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 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.
期刊介绍：
Acta Oncologica is a journal for the clinical oncologist and accepts articles within all fields of clinical cancer research. Articles on tumour pathology, experimental oncology, radiobiology, cancer epidemiology and medical radio physics are also welcome, especially if they have a clinical aim or interest. Scientific articles on cancer nursing and psychological or social aspects of cancer are also welcomed. Extensive material may be published as Supplements, for which special conditions apply.
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