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.

Autor:	Nitz UA; West German Study Group GmbH, Moenchengladabach; Evangelical Hospital Johanniter Bethesda, Breast Center Niederrhein, Moenchengladbach., Gluz O; West German Study Group GmbH, Moenchengladabach; Evangelical Hospital Johanniter Bethesda, Breast Center Niederrhein, Moenchengladbach; University of Cologne, Cologne. Electronic address: oleg.gluz@wsg-online.com., Christgen M; Institute of Pathology, Medical School Hannover, Hannover., Grischke EM; Department of Gynecology and Obstetrics, University Clinics Tuebingen, Tuebingen., Augustin D; Breast Center Ostbayern, Deggendorf., Kuemmel S; Breast Center, Clinics Essen-Mitte, Essen., Braun M; Rotkreuz Clinics Munich Breast Center, Munich., Potenberg J; Department of Oncology Evangelical Waldkrankenhaus Berlin, Berlin., Kohls A; Department of Gynecology and Obstetrics, Evangelical Hospital, Ludwigsfelde., Krauss K; Department of Gynecology and Obstetrics, University Clinics RWTH, Aachen., Stefek A; Breast Center, Evangelical Hospital Johanniter, Stendal., Schumacher C; Breast Center, St. Elisabeth Hospital Cologne, Cologne., Forstbauer H; Oncology Practice Network, Troisdorf., Reimer T; Department of Gynecology and Obstetrics, University Clinics Rostock, Suedstadt., Fischer H; Breast Center, Evangelical Hospital Gelsenkirchen, Gelsenkirchen., Liedtke C; Department of Gynecology and Obstetrics, University Clinics Schleswig-Holstein/Campus Luebeck, Luebeck; Charite Berlin., Wuerstlein R; Breast Center, Department of Gynecology and Obstetrics, University of Munich (LMU) and CCCLMU, Munich., Schumacher J; Palleos Healthcare, Statistics, Wiesbaden, Germany., Kates R; West German Study Group GmbH, Moenchengladabach., Kreipe H; University of Cologne, Cologne., Harbeck N; West German Study Group GmbH, Moenchengladabach; Breast Center, Department of Gynecology and Obstetrics, University of Munich (LMU) and CCCLMU, Munich.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2017 Nov 01; Vol. 28 (11), pp. 2768-2772.
DOI:	10.1093/annonc/mdx494
Abstrakt:	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 and Methods: Female patients with HER2+/HR- EBC (M0) were randomized (5:2) 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. (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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