De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel.
Ann Oncol
; 28(11): 2768-2772, 2017 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-28945833
ABSTRACT
BACKGROUND:
Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy. PATIENTS ANDMETHODS:
Female patients with HER2+/HR- EBC (M0) were randomized (52) to 12 weeks of T + P ± weekly paclitaxel (pac) at 80 mg/m2. Early response was defined as proliferation decrease ≥30% of Ki-67 (versus baseline) or low cellularity (<500 invasive tumor cells) in the 3-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T + P arm versus all chemotherapy-treated patients.RESULTS:
From February 2014 to December 2015, 160 patients were screened, 92 were randomized to T + P and 42 to T + P+pac. Baseline characteristics were well balanced (median age 54 versus 51.5 years, cT2 51.1 versus 52.4%, cN0 54.3 versus 61.9%); 91.3% of patients completed T + P per protocol and 92.9% T + P+pac. The pCR rate in the T + P+pac arm was 90.5%, compared with 36.3% in the T + P arm as a whole. In the T + P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared with 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92). No new safety signals were observed in the study population.CONCLUSION:
Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared with dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.Palavras-chave
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Assunto principal:
Neoplasias da Mama
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Protocolos de Quimioterapia Combinada Antineoplásica
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Biomarcadores Tumorais
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Receptor ErbB-2
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Terapia Neoadjuvante
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article