De-escalation of Neoadjuvant Treatment (Paclitaxel + HP) in Early HER2+ Breast Cancer

Summary

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.

Conditions

• Breast Cancer
• HER2-positive Breast Cancer
• Early Breast Cancer

Interventions

DRUG

Paclitaxel

80 mg/m2 IV weekly for 12 weeks

DRUG

trastuzumab

Loading dose 8 mg/kg, then 6 mg/kg IV every 3 weeks

DRUG

Pertuzumab

Loading dose 840 mg, then 420 mg IV every 3 weeks

DRUG

Docetaxel

75 mg/m2 IV every 3 weeks for 6 cycles

DRUG

carboplatin

AUC 6 IV every 3 weeks for 6 cycles

PROCEDURE

Radical Surgery

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).

DRUG

Adjuvant Systemic Therapy

Risk-adapted post-neoadjuvant treatment based on pathological response: * Patients with pCR (ypT≤1a, ypN0, RCB 0-I) receive Trastuzumab to complete 1 year of anti-HER2 therapy (combined with endocrine therapy for luminal subtypes). * Patients with residual disease (ypT≥1b and/or ypN+ and/or RCB II-III) receive Trastuzumab emtansine (T-DM1) 3.6 mg/kg every 3 weeks for up to 14 cycles (combined with endocrine therapy for luminal subtypes). Adjuvant radiotherapy is administered if clinically indicated.

Sponsors & Collaborators

• National Medical Research Radiological Centre of the Ministry of Health of Russia

  lead OTHER

Principal Investigators

• Larisa Bolotina, MD, PhD · P.A. Hertsen Moscow Oncology Research Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-09-01

Primary Completion

2025-12-10

Completion

2028-12-30

Countries

• Russia

Study Locations