A Prospective, Randomized Multicenter, Open-label Comparison of Preoperative Combination of Trastuzumab and Pertuzumab With or Without Concurrent Taxane Chemotherapy Given for Twelve Weeks in Patients With Operable HER2+/HR- Breast Cancer Within the ADAPT Protocol

Conditions

Breast Cancer

Brief summary

Trial to evaluate efficacy of dual blockade with two anti-HER2 agents with or without chemotherapy backbone within the ADAPT trial.

Monika Graeser, Oleg Gluz, Christine zu Eulenburg, Sherko Kuemmel, Matthias Christgen et al. (20 authors)

Journal of Clinical Oncology2025-05-281 citations

10.1200/jco.2025.43.16_suppl.502

Abstract PS09-01: Individual patient data meta-analysis of clinical and translational biomarkers for prediction of pathological complete response (pCR) after de-escalated therapy in HER2+ breast cancer in four trials of the West German Study Group

Monika Graeser, Oleg Gluz, Christine zu Eulenburg, Sherko Küemmel, Raquel von Schumann et al. (25 authors)

Cancer Research2024-05-02

10.1158/1538-7445.sabcs23-ps09-01

Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial

Monika Graeser, Oleg Gluz, Claudia Biehl, Daniel Ulbrich-Gebauer, Matthias Christgen et al. (27 authors)

Clinical Cancer Research2022-11-2813 citations

10.1158/1078-0432.ccr-22-1587

De-escalated neoadjuvant pertuzumab plus trastuzumab therapy with or without weekly paclitaxel in HER2-positive, hormone receptor-negative, early breast cancer (WSG-ADAPT-HER2+/HR-): survival outcomes from a multicentre, open-label, randomised, phase 2 trial.

Nitz U, Gluz O, Graeser M, Christgen M, Kuemmel S, Grischke EM, Braun M, Augustin D, Potenberg J, Krauss K, Schumacher C, Forstbauer H, Reimer T, Stefek A, Fischer HH, Pelz E, Zu Eulenburg C, Kates R, Wuerstlein R, Kreipe HH, Harbeck N, WSG-ADAPT investigators.

2022-04-0859 citations

10.1016/s1470-2045(22)00159-0

Magnetic resonance imaging and ultrasound for prediction of residual tumor size in early breast cancer within the ADAPT subtrials.

Graeser M, Schrading S, Gluz O, Strobel K, Herzog C, Umutlu L, Frydrychowicz A, Rjosk-Dendorfer D, Würstlein R, Culemann R, Eulenburg C, Adams J, Nitzsche H, Prange A, Kümmel S, Grischke EM, Forstbauer H, Braun M, Potenberg J, von Schumann R, Aktas B, Kolberg-Liedtke C, Harbeck N, Kuhl CK, Nitz U.

2021-03-188 citations

10.1186/s13058-021-01413-y

Impact of PIK3CA mutation status on immune marker response and pCR in the WSG-ADAPT HER2+/HR+ phase II trial.

Nadia Harbeck, Ulrike Nitz, Matthias Christgen, Ronald Kates, Michael Wilhelm Braun et al. (20 authors)

Journal of Clinical Oncology2018-05-201 citations

10.1200/jco.2018.36.15_suppl.572

WSG ADAPT - adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer: study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III trial.

Hofmann D, Nitz U, Gluz O, Kates RE, Schinkoethe T, Staib P, Harbeck N.

2013-08-1985 citations

10.1186/1745-6215-14-261

Interventions

DRUGTrastuzumab

DRUGPertuzumab

DRUGPaclitaxel

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly) * Histologically confirmed unilateral primary invasive carcinoma of the breast * Clinical T1 - T4 (except inflammatory breast cancer) * All clinical N (cN) * No clinical evidence for distant metastasis (M0) * Known HR status and HER2 status (local pathology) Tumor block available for central pathology review * Performance Status ECOG ≤ 1 or KI ≥ 80% * Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients * Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements * The patient must be accessible for treatment and follow-up Additional Inclusion criteria for participation in the HR-/HER2+ sub-protocol: * Confirmed ER and PR negative and HER2+ by central pathology * Clinical cT1c - T4a-c (participation of patients with tumors \>cT2 is strongly recommended) * All clinical N (participation of patients with cN0, if at least cT1c is strongly recommended) * Patients must qualify for neoadjuvant treatment * LVEF \> 50%; LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to induction treatment)

Exclusion criteria

* Known hypersensitivity reaction to the compounds or incorporated substances * Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri * Non-operable breast cancer including inflammatory breast cancer * Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor * Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry * Male breast cancer * Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment * Breast feeding woman * Sequential breast cancer * Reasons indicating risk of poor compliance Patient not able to consent Additional

Design outcomes

Primary

Measure	Time frame	Description
Definition of a biomarker (profile) characterizing good responders to dual blockade T and P anti-HER2 blockade that have similar pCR rates as patients treated with identical dual anti-HER2 blockade + taxane backbone	After 12 weeks of therapy	pCR will be measured after 12 weeks of randomized treatment.

Countries

Germany

Outcome results

None listed