Efficacy of Endocrine Therapy Plus Trastuzumab and Pertuzumab vs De-escalated Chemotherapy in Patients with Hormone Receptor-Positive/ERBB2-Positive Early Breast Cancer: The Neoadjuvant WSG-TP-II Randomized Clinical Trial.

Importance: Combination of chemotherapy with (dual) ERBB2 blockade is considered standard in hormone receptor (HR)-positive/ERBB2-positive early breast cancer (EBC). Despite some promising data on endocrine therapy (ET) combination with dual ERBB2 blockade in HR-positive/ERBB2-positive BC, to our knowledge, no prospective comparison of neoadjuvant chemotherapy vs ET plus ERBB2 blockade in particular with focus on molecular markers has yet been performed.

Objective: To determine whether neoadjuvant de-escalated chemotherapy is superior to endocrine therapy, both in combination with pertuzumab and trastuzumab, in a highly heterogeneous HR-positive/ERBB2-positive EBC.

Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

Background: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection.

Patients And Methods: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m q2w or 8× nab-paclitaxel 125 mg/m q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25.

De-Escalated Neoadjuvant Trastuzumab-Emtansine With or Without Endocrine Therapy Versus Trastuzumab With Endocrine Therapy in HR+/HER2+ Early Breast Cancer: 5-Year Survival in the WSG-ADAPT-TP Trial.

Purpose: Neoadjuvant chemotherapy is standard of care in human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), irrespective of the hormone receptor status. Trastuzumab-emtansine (T-DM1), antibody-drug conjugate, is highly effective in HER2+ EBC; however, no survival data are available for de-escalated antibody-drug conjugate-based neoadjuvant therapy without conventional chemotherapy.

Patients And Methods: In the WSG-ADAPT-TP (ClinicalTrials.

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.

Purpose: To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2+/HR- trial (NCT01817452).

Experimental Design: Patients with cT1-cT4c, cN0-3 HER2+/HR- early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n = 92) or P+T+paclitaxel (n = 42). Gene expression signatures were analyzed in baseline biopsies using NanoString Breast Cancer 360 panel (n = 117); baseline and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively.

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.

Background: Several de-escalation neoadjuvant strategies have been investigated to reduce the use of chemotherapy in HER2-positive early breast cancer using pathological complete response as a surrogate endpoint; there are few survival data from these trials. Here, we report 5-year survival data in the WSG-ADAPT-HER2+/HR- trial and address the effect of pathological complete response, early therapy response, and molecular subtype.

Methods: WSG-ASAPT-HER2+/HR-, a part of the ADAPT umbrella trial performed in patients with different subtypes of early breast cancer, was an investigator-initiated, multicentre, open-label, randomised, phase 2 trial done at 40 Breast Cancer Centres in Germany.