Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial.
Breast Cancer Res Treat
; 205(2): 267-279, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38453781
ABSTRACT
PURPOSE:
Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status.METHODS:
Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m2 then 100mg/m2). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m2) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier's classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity.RESULTS:
Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI 58.9-85.4) vs. 71.9% (95%CI 54.6-84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI 53.8-83.2) vs. 61.5% (95%CI 42.5-77.6), 82.4% (95%CI 62.2-93.6) vs. 100% (95%CI 74.1-100), and 90% (95%CI 69.8-98.3) vs. 100% (95%CI 74.1-100). Toxicity profile was consistent with previous reports.CONCLUSION:
Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned. TRIAL REGISTRATION NUMBER NCT02339532 (registered on 14/12/14).Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Protocolos de Quimioterapia Combinada Antineoplásica
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Carboplatina
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DNA Topoisomerases Tipo II
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Receptor ErbB-2
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Terapia Neoadjuvante
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Anticorpos Monoclonais Humanizados
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Trastuzumab
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Docetaxel
Idioma:
En
Revista:
Breast Cancer Res Treat
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França