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| ID | Type | Description | Link |
|---|---|---|---|
| LEC #962/107 | Other Identifier | Ethics Council, P.A. Hertsen MORI |
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This phase II study evaluates the efficacy and safety of a de-escalated neoadjuvant chemotherapy regimen in patients with early-stage HER2-positive breast cancer. The experimental regimen consists of 12 weekly cycles of paclitaxel combined with trastuzumab and pertuzumab (THP), without anthracyclines.
The study aims to determine if this less toxic regimen can achieve high rates of pathological complete response (pCR) comparable to standard anthracycline-containing regimens. The results are compared with a historical control group of patients who received the standard TCHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab).
A total of 186 participants are included in the analysis: 93 patients prospectively treated with the de-escalated THP regimen and 93 patients in the retrospective historical control group (TCHP). The primary endpoint is the pCR rate at the time of surgery. Secondary endpoints include toxicity, rate of breast-conserving surgery, and 3-year event-free survival.
Background:
Standard neoadjuvant therapy for HER2-positive breast cancer often includes anthracyclines (AC-THP) or platinum-based regimens (TCHP), which are associated with significant toxicity. De-escalation strategies aim to reduce toxicity without compromising efficacy, particularly in patients with early-stage disease.
Study Design:
This is an investigator-initiated, single-center, open-label, non-randomized phase II study.
Primary Objective:
To evaluate the pathological complete response (pCR, ypT0/is ypN0) rate in the de-escalated arm.
Secondary Objectives:
The study hypothesis is that the de-escalated THP regimen provides a favorable toxicity profile while maintaining high efficacy in a selected population of early HER2+ breast cancer patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental: De-escalated THP | Experimental | Patients receive de-escalated neoadjuvant chemotherapy consisting of 12 weekly cycles of Paclitaxel combined with Trastuzumab and Pertuzumab (THP regimen), followed by surgery. |
|
| Historical Control: Standard TCHP | Active Comparator | Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Paclitaxel | Drug | 80 mg/m2 IV weekly for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathological Complete Response (pCR) Rate | Defined as the absence of invasive cancer in the breast and axillary lymph nodes (ypT0/is ypN0) at the time of surgery | At the time of surgery (approximately 12-18 weeks after treatment initiation) |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Grade 3-4 Adverse Events | Assessment of treatment-related toxicity (neutropenia, diarrhea, etc.) according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death. | From first dose until 30 days after last dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Larisa Bolotina, MD, PhD | P.A. Hertsen Moscow Oncology Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| P.A. Hertsen Moscow Oncology Research Institute | Moscow | 125284 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28945833 | Background | Nitz UA, Gluz O, Christgen M, Grischke EM, Augustin D, Kuemmel S, Braun M, Potenberg J, Kohls A, Krauss K, Stefek A, Schumacher C, Forstbauer H, Reimer T, Fischer H, Liedtke C, Wuerstlein R, Schumacher J, Kates R, Kreipe H, Harbeck N. 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. Ann Oncol. 2017 Nov 1;28(11):2768-2772. doi: 10.1093/annonc/mdx494. | |
| 35538105 |
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Individual participant data will not be shared due to patient confidentiality requirements
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Prospective single-arm de-escalation cohort compared with a retrospective historical control cohort.
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| trastuzumab | Drug | Loading dose 8 mg/kg, then 6 mg/kg IV every 3 weeks |
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| Pertuzumab | Drug | Loading dose 840 mg, then 420 mg IV every 3 weeks |
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| Docetaxel | Drug | 75 mg/m2 IV every 3 weeks for 6 cycles |
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| carboplatin | Drug | AUC 6 IV every 3 weeks for 6 cycles |
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| Radical Surgery | Procedure | Standard radical resection (mastectomy or breast-conserving surgery) with axillary staging (sentinel lymph node biopsy and/or axillary lymph node dissection [Levels I-II], according to current clinical guidelines). |
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| Adjuvant Systemic Therapy | Drug | Risk-adapted post-neoadjuvant treatment based on pathological response:
Adjuvant radiotherapy is administered if clinically indicated. |
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| Rate of Breast-Conserving Surgery | Proportion of patients eligible for and undergoing breast-conserving surgery | At the time of surgery |
| 3-Year Event-Free Survival (EFS) | Time from enrollment to disease progression, local recurrence, distant metastasis, or death from any cause | 3 years from enrollment |
| Background |
| Waks AG, Desai NV, Li T, Poorvu PD, Partridge AH, Sinclair N, Spring LM, Faggen M, Constantine M, Metzger O, Alberti J, Deane J, Rosenberg SM, Frank E, Tolaney SM, Krop IE, Tung NM, Tayob N, King TA, Mittendorf EA, Winer EP. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022 May 10;8(1):63. doi: 10.1038/s41523-022-00429-7. |
| 23704196 | Background | Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. doi: 10.1093/annonc/mdt182. Epub 2013 May 22. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| D000068878 | Trastuzumab |
| C485206 | pertuzumab |
| D000077143 | Docetaxel |
| D016190 | Carboplatin |
| D000080044 | Ado-Trastuzumab Emtansine |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D008453 | Maytansine |
| D018942 | Macrolides |
| D007783 | Lactones |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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