Neoadjuvant Therapy With Trastuzumab and Chemotherapy and the Resultant Pathologic Complete Response Observed in HER2 Positive Breast Cancer;a Systematic Review

June 26, 2023 updated by: Maham Leeza Adil, Rawalpindi Medical College

The goal of this systematic review is to assess the effectiveness of neoadjuvant chemotherapy and Trastuzumab in achieving pathological complete response (pCR) in patients with HER2-positive breast cancer. The main questions it aims to answer are:

  • What is the overall rate of pathological complete response (pCR) in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy and Trastuzumab?
  • Are there any variations in the definition of pCR among the included trials?

Participants in the selected clinical trials were HER2-positive breast cancer patients with non-metastatic operable, locally advanced, or inflammatory breast cancer. The main tasks participants were asked to do and the treatments they received are as follows:

  • Undergo neoadjuvant chemotherapy: Participants received chemotherapy treatment before their primary surgery.
  • Receive Trastuzumab: Participants were administered Trastuzumab, a targeted therapy for HER2-positive breast cancer.

Researchers would compare the group of participants receiving neoadjuvant chemotherapy and Trastuzumab to other groups, if present, to see if there are differences in the rates of pathological complete response (pCR) or other effects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This systematic review aimed to assess the effectiveness of neoadjuvant chemotherapy and Trastuzumab in achieving pathological complete response (pCR) in patients with HER2-positive breast cancer. The researchers identified nine clinical trials that met the inclusion criteria. These trials included patients with non-metastatic operable, locally advanced, or inflammatory breast cancer, and they evaluated the pCR as the primary or secondary endpoint.

The trials utilized different chemotherapy and targeted therapy regimens, along with varying dosages of Trastuzumab. The primary outcome of interest was the pCR rate, while other survival outcomes were not analyzed. Among the 1,209 patients who received neoadjuvant chemotherapy and Trastuzumab, the overall pCR rate was found to be 42%.

The review provided detailed information about the design of the selected trials, patient characteristics, disease staging, HER2 status, administered treatment regimens, and primary/secondary endpoints. It also mentioned slight variations in the definition of pCR across the trials.

Study Type

Observational

Enrollment (Actual)

1209

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Punjab
      • Rawalpindi, Punjab, Pakistan, 46000
        • Rawalpindi Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

This study only included clinical trials. The review methods were decided before the start of the review. Studies that used the pathological complete response (pCR) as their primary or secondary endpoint were considered. The proportion of patients without invasive breast and axillary cancer was the criteria used to define pCR (ypT0/is and ypN0).

Patients with breast cancer that was found to be HER2 positive were included. If the HER2 FISH test score was 2 or higher or the immunohistochemistry score for HER2 was +3, the HER2 status was interpreted as positive.

Description

Inclusion Criteria:

  • Patients with breast cancer that was found to be HER2 positive were included
  • Only patients who underwent neoadjuvant therapy were included
  • All cytotoxic chemotherapy regimens were considered eligible for this systematic review given that the same drugs were given at the same dose in every trial.

Exclusion Criteria:

  • Patients with metastatic breast cancer were not included in the systematic review
  • Results from adjuvant therapy were excluded from this study.
  • Only the most recent publication (and the most informative) was included if numerous publications of the same trial were retrieved or if there was a case mix between publications.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group recieving Trastuzumab + Chemotherapy
Two different treatment regimens of Trastuzumab were giving in the 9 studies Dosage of trastuzumab was 4 mg/kg loading dose followed by 2 mg/kg every 3 weeks in four clinical trials included in this systematic review Dosage of trastuzumab was 8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks in five clinical trials included in this systematic review The different chemotherapeutic agents given included Paclitaxel, docetaxel, fluorouracil, epirubicin, carboplatin, cyclophosphamide, methotrexate, and fluorouracil.
Drug: Trastuzumab
Trastuzumab was given at dosage of either 4mg/kg or 8mg/kg at mostly a weekly interval (but differs among the different studies)
Group receiving chemotherapy
Different neoadjuvant chemotherapy regimens were given in the nine clinical trials included in this systematic review. The different chemotherapeutic agents given included Paclitaxel, docetaxel, fluorouracil, epirubicin, carboplatin, cyclophosphamide, methotrexate, and fluorouracil.
Drug: Trastuzumab
Trastuzumab was given at dosage of either 4mg/kg or 8mg/kg at mostly a weekly interval (but differs among the different studies)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response (pCR)
Time Frame: 5 years
5 trials labelled pCR as the absence of residual invasive cancer in the breast and lymph nodes while 4 trials defined pCR as the absence of invasive neoplastic cells at microscopic examination of the primary tumour at surgery
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rawalpindi Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2023

Primary Completion (Actual)

June 15, 2023

Study Completion (Actual)

June 18, 2023

Study Registration Dates

First Submitted

June 26, 2023

First Submitted That Met QC Criteria

June 26, 2023

First Posted (Actual)

July 5, 2023

Study Record Updates

Last Update Posted (Actual)

July 5, 2023

Last Update Submitted That Met QC Criteria

June 26, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 823678

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No patient data to be shared

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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