Study to Compare Neoadjuvant Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy and Quality of Life Assessment Under Adjuvant Therapy in Operable HER2+/HR+ Breast Cancer Patients

Conditions

Breast Neoplasms

Keywords

hormone receptor positive, human epidermal growth factor receptor 2 positive, Early breast cancer, HR+/HER2+

Brief summary

This is a prospective, phase IIa, multicenter, randomized, open-label study comparing a pre-surgical combination of trastuzumab and pertuzumab with concurrent weekly paclitaxel chemotherapy or endocrine therapy given for 12 weeks with a quality of life assessment for 40 additional weeks in patients with operable HER2+/HR+ breast cancer.

O Gluz, Ulrike A. Nitz, Matthias Christgen, Sherko Kuemmel, Johannes Holtschmidt et al. (17 authors)

Journal of Clinical Oncology2026-05-18

10.1200/jco-25-01047

Prediction of survival after de-escalated neoadjuvant therapy in HER2+ early breast cancer: A pooled analysis of three WSG trials.

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

Gene expression signatures, stromal tumor infiltrating lymphocytes (sTILs), and change in tumor cellularity to predict pathological complete response (pCR) after 12 week de-escalated neoadjuvant endocrine therapy (ET) vs paclitaxel + dual HER2 blockade in the WSG-TP-II trial.

Monika Graeser, Oleg Gluz, Ulrike Nitz, Claudia Biehl, Angela Berg et al. (20 authors)

Journal of Clinical Oncology2023-06-012 citations

10.1200/jco.2023.41.16_suppl.519

Efficacy of Endocrine Therapy Plus Trastuzumab and Pertuzumab vs De-escalated Chemotherapy in Patients with Hormone Receptor–Positive/<i>ERBB2</i>-Positive Early Breast Cancer

Oleg Gluz, Ulrike Nitz, Matthias Christgen, Sherko Küemmel, Johannes Holtschmidt et al. (20 authors)

JAMA Oncology2023-05-1127 citations

10.1001/jamaoncol.2023.0646

De-escalated chemotherapy versus endocrine therapy plus pertuzumab+ trastuzumab for HR+/HER2+ early breast cancer (BC): First efficacy results from the neoadjuvant WSG-TP-II study.

Oleg Gluz, Ulrike Nitz, Matthias Christgen, Sherko Küemmel, Johannes Holtschmidt et al. (17 authors)

Journal of Clinical Oncology2020-05-2014 citations

10.1200/jco.2020.38.15_suppl.515

Trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first-line or second-line treatment for HER2-positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non-inferiority, phase III trial in Japan (JBCRG-M06/EMERALD).

Yamashita T, Masuda N, Saji S, Araki K, Ito Y, Takano T, Takahashi M, Tsurutani J, Koizumi K, Kitada M, Kojima Y, Sagara Y, Tada H, Iwasa T, Kadoya T, Iwatani T, Hasegawa H, Morita S, Ohno S.

2020-05-0712 citations

10.1186/s13063-020-04341-y

Interventions

DRUGPerjeta Injectable Product

Single dose of 840mg (loading dose) day1 cycle 1, 420mg at day1 of each subsequent cycle, every 3 weeks. (The latter cycle is called cycle of treatment and is to be given 4 times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)

DRUGHerceptin

Single dose of 8mg/kg (loading dose) day1 cycle 1; 6mg/kg at day1 of each subsequent cycle body weight every 3 weeks. (This is called cycle of treatment and is to be given four times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)

DRUGTamoxifen

20 mg per day for a total of 40 weeks in the adjuvant therapy phase.

DRUGPaclitaxel

80mg/sqm, day one of each cycle, every week. This is called a cycle of treatment and is to be given for 12 weeks in neoadjuvant therapy phase.

DRUGEpirubicin

12 weeks (4cycles) of max. 90mg/sqm in adjuvant therapy phase

DRUGCyclophosphamide

12 weeks (4cycles) of 600 mg/sqm i.v. on day 1+8 or 12 weeks (4cycles) of 500 mg/sqm i.v. on day 1 in adjuvant therapy phase

DRUGAnastrozole

1mg per day for a total of 40 weeks in adjuvant therapy phase

DRUGLetrozole

2,5 mg/day for a total of 40 weeks in adjuvant therapy phase

DRUGExemestane

25mg/day for a total of 40 weeks in adjuvant therapy phase

DRUGLeuprorelin acetate

One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.

DRUGGoserelin

3,6mg every 28 days or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.

DRUGLeuporelin acetate

One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase).

DIAGNOSTIC_TESTBiopsy

Core biopsy at screening (outside of protocol), at week 4 after randomization, (at week 14 in addition if neoadjuvant phase is prolonged)

PROCEDURESurgery

Surgery at week 14 after randomization (or later, if neoadjuvant phase is prolonged)

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 older * Histologically confirmed unilateral primary invasive carcinoma of the breast * Patients must qualify for neoadjuvant treatment as follows: * No clinical evidence for distant metastasis (M0) * Clinical cT1c-T4a-c (participation of patients with tumors \> cT2 is strongly recommended) and no evidence for distant metastases (M0) * All clinical N (participation of patients with cN+, also in case of cT1c, is strongly recommended) * Known positive HR-status and centrally confirmed HER2+-status by IHC/FISH * Patients need to fulfill adequate blood count and organ function to receive chemotherapy (see

Exclusion criteria

). * 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 registration in premenopausal patients * Patients of childbearing potential must accept to implement a highly effective (less than 1% failure rate according to Pearl index) non-hormonal contraceptive measures during the study treatment and for 6 months following the last dose of study treatment (trastuzumab and pertuzumab) such as: * Intrauterine device (IUD) * bilateral tubal occlusion * vasectomised partner * sexual abstinence * 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 * LVEF \> 55%; LVEF within normal limits of each institution measured by echocardiography (within 42 days prior to randomization) * Normal ECG (within 42 days prior to randomization)

Design outcomes

Primary

Measure	Time frame	Description
Pathological complete response (pCR)	14 weeks after start of therapy treatment	14 weeks after start of therapy treatment, tumor and lymph node biopsy is performed to reach the primary endpoint of pathological complete response (pCR) which is defined as the absence of residual invasive cancer of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ypT0/is ypN0 in the current AJCC staging system). As secondary endpoint, also other response states will be taken into account: no invasive tumor in the complete resected breast specimen irrespective of the lymph node state following completion of neoadjuvant systemic therapy (ypT0/is, any ypN).

Secondary

Measure	Time frame	Description
Health-related quality of life using EQ5D-5L scale	During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first	* questions about self care, usual activities, pain /discomfort, anxiety/depression are assessed on a 5 level-scale using tick boxes : I have no problem; I have slight problems; I have moderate problems; I have severe problems I am unable * assessment of the patient health (good or bad) is measured on a scale numbered from 0 to 100 (100 means the best heath and 0 means the worst)
Health-related quality of life using EORTC QLQ-C30 scale	During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first	* Assessment of quality of life questions (activities, breath, pain, sleep, appetite, vomiting, constipation, others..) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much) * Assessment of Overall health and overall quality of life during the past week is measured on a 7 level-scale going from 1 (very poor) to 7 (excellent)
Tumor size reduction by mammography	at screening visit and 12 weeks after start of therapy treatment	The diameters of the tumors in the breast will be measured in millimeter by mammography as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
Tumor size reduction by palpation and ultrasound	at screening visit and 4, 7 and 13 weeks after start of therapy treatment	The diameters of the tumors in the breast will be measured in millimeter by palpation and ultrasound as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
Health-related quality of life using EORTC QBL-BR-23 scale	During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first	Assessment of quality of life questions during the past week or during the past 4 weeks (depending on the questions) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)
Duration of invasive disease-free survival	From date of treatment allocation until the date of first documented progression or secondary tumor or date of death from any cause, whichever came first, assessed up to 60 months (study duration including follow up)	Duration of invasive disease-free survival is defined as time (days) between study treatment allocation and relapse, secondary tumor event or death.
Number of mastectomies	14 weeks after start of therapy treatment	The number of mastectomies will be determined at time of surgery (week 14 and week 18)
Ki67 level	4 weeks after start of therapy treatment	The level of Ki67 in biopsie material will be measured at week 4 of neoadjuvant therapy
cDNA composition	at baseline, 3 weeks, 4 weeks and 6, 18, 24, 36 48 and 60 months after start of therapy treatment	The composition of cDNA in blood samples will be measured
Overall survival	From date of randomization until the date of death from any cause, assessed up to 60 months	The overall survival is defined as time (days) between study treatment allocation and death of patient due to any cause.

Countries

Germany

Outcome results

None listed