West German Study Group
ADAPT-HER2-IV will address question of optimal neoadjuvant therapy in patients with less advanced -HER2+ EBC. ADAPT-HER2-IV is planned as a superiority trial to demonstrate higher pCR rates in both clinically relevant subgroups of low-intermediate risk HER2+ EBC. Moreover, it aims to demonstrate excellent survival in patients treated by T-DXd (with the use of standard chemotherapy at investigator´s decision restricted only to patients with substantial residual tumour burden after T-DXd-treatment).
HER2-positive Early Breast Cancer
Trastuzumab deruxtecan
Standard-of-Care
Phase 2
As the ADAPT-trials have clearly shown, pCR after 12 weeks of therapy, independent of the specific de-escalated neoadjuvant regimen and independent of further use of systemic chemotherapy, is an independent predictor of excellent prognosis4,19, also in patients treated by an antibody-drug conjugate alone (T-DM1), or in those receiving pertuzumab+trastuzumab+/-weekly paclitaxel. In contrast to the adjuvant setting, none of the neoadjuvant trials so far has focused on HER2+ patients with a low-intermediate risk profile (e.g., node-negative patients with cT1-2 tumours). The ADAPT-HER2-IV trial aims to close this evidence gap. Since there is some uncertainty about the optimal treatment duration in intermediate- to high-risk HER2+ EBC (e.g., tumour size >3 cm), we recommend using a longer 18-week taxane-based treatment (+/- carboplatin, at investigator´s decision) due to a large body of evidence for taxane + carboplatin combinations in patients in locally advanced stages. Antibody-drug conjugates appear to be ideal candidate drugs for a "de-escalated" treatment due to their favourable safety (reduced alopecia, polyneuropathy rates, etc.) and a high efficacy profile (e.g., comparable pCR rates after 18 weeks of T-DM1 and taxane+pertuzumab+trastuzumab in the PREDIX HER2 trial20). Similarly to the classical chemotherapy landscape, optimal duration of antibody-drug conjugate-based neoadjuvant therapy remains unclear. pCR rates of around 40% to 60% were observed after 12 and 18 weeks of T-DM1 treatment (+/-pertuzumab) in the ADAPT TP, KRISTINE and PREDIX HER2 trials in HR+/HER2+ disease21,22. Moreover, long-term survival seem to be comparable between T-DM1+pertuzumab and older chemotherapy-containing regimens (docetaxel+carboplatin+trastuzumab+pertuzumab) despite of higher local progression rates and lower pCR in one study22. Trastuzumab-deruxtecan (T-DXd) has shown promising activity in a small cohort of metastatic patients, including both HER2+ and HER2-low BC, pre-treated with several lines of therapy. Doi et al. reported overall response rates (ORR) of 58% and a disease control rate of 100% with overall survival at 12 months at in HER2+ disease pre-treated by T-DM1+/-pertuzumab in a late line setting23. T-DXd-therapy was associated with a manageable safety profile. Recently, clearly higher efficacy of T-DXd vs. T-DM1 was shown in second line metastatic breast cancer (MBC) in the DESTINY-03 trial24. Median progression free survival was not reached in T-DM1-arm vs. 6.8 months in the T-DXd-arm. This effect was independent of hormone receptor status, prior pertuzumab treatment, visceral metastases, number of prior therapy lines and presence of brain metastases. ORR was doubled (34.2 vs. 79.7%), favouring the T-DXd arm.
Study Type : | Interventional |
Estimated Enrollment : | 402 participants |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | NeoAdjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Trastuzumab-deruxtecan Versus Pacli-/Docetaxel+Carboplatin+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer |
Actual Study Start Date : | December 2023 |
Estimated Primary Completion Date : | June 2026 |
Estimated Study Completion Date : | June 2028 |
Arm | Intervention/treatment |
---|---|
Experimental: T-DXd: HER2+ and low-intermediate risk for recurrence 12 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment |
Drug: Trastuzumab deruxtecan |
Experimental: T-DXd: HER2+ and intermediate-high risk for recurrence 18 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment |
Drug: Trastuzumab deruxtecan |
Other: Control: HER2+ and low-intermediate risk for recurrence Standard-of-Care-Treatment: 12 weeks PAC+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment |
Drug: Standard-of-Care |
Other: Control: HER2+ and intermediate-high risk for recurrence Standard-of-Care-Treatment: 18 weeks PAC/DOC+Carbo+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment |
Drug: Standard-of-Care |
Ages Eligible for Study: | 18 Years |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
Not yet recruiting
Breast Center of the University of Munich (LMU) Universitätsfrauenklinik
Munich, Bavaria, Germany, 81377
Not yet recruiting
Rotkreuz Klinikum München
Muenchen, Bayern, Germany, 80637
Not yet recruiting
Niels-Stensen-Kliniken Franziskus-Hospital
Georgsmarienhütte, Niedersachsen, Germany, 49124
Not yet recruiting
Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum
Essen, NRW, Germany, 45136
Not yet recruiting
Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus
Moenchengladbach, NRW, Germany, 41061
Not yet recruiting
Klinikum Mittelbaden, Brustzentrum
Baden-Baden, Germany, 33604
Not yet recruiting
Onkologische Schwerpunktpraxis Bielefeld
Bielefeld, Germany,
Not yet recruiting
Universitätsklinikum Essen, Burstzentrum
Essen, Germany,
Not yet recruiting
Onkodok Gütersloh
Gütersloh, Germany,
Not yet recruiting
Brustzentrum am Krankenhaus Jerusalem
Hamburg, Germany,
Not yet recruiting
St. Barbara Klinik
Hamm, Germany,
Not yet recruiting
Helios-Klinik Wuppertal
Wuppertal, Germany,