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

NCT05931042 | Completed DMC FDA Drug

• 1 other identifier: 823678
• Study Type: observational
• Target: 1,209
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HER2+ Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  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

Study Arms (2)

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

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

Interventions

Trastuzumab DRUG

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; Group recieving Trastuzumab + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients found to have HER2+ breast cancer were included
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rawalpindi Medical College: lead

Study Sites (1)

Rawalpindi Medical University

Rawalpindi, Punjab Province, 46000, Pakistan

Location

Related Publications (9)

• I-SPY2 Trial Consortium; Yee D, DeMichele AM, Yau C, Isaacs C, Symmans WF, Albain KS, Chen YY, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal IT, Tawfik O, LeBeau LG, Sahoo S, Vinh T, Chien AJ, Forero-Torres A, Stringer-Reasor E, Wallace AM, Pusztai L, Boughey JC, Ellis ED, Elias AD, Lu J, Lang JE, Han HS, Clark AS, Nanda R, Northfelt DW, Khan QJ, Viscusi RK, Euhus DM, Edmiston KK, Chui SY, Kemmer K, Park JW, Liu MC, Olopade O, Leyland-Jones B, Tripathy D, Moulder SL, Rugo HS, Schwab R, Lo S, Helsten T, Beckwith H, Haugen P, Hylton NM, Van't Veer LJ, Perlmutter J, Melisko ME, Wilson A, Peterson G, Asare AL, Buxton MB, Paoloni M, Clennell JL, Hirst GL, Singhrao R, Steeg K, Matthews JB, Asare SM, Sanil A, Berry SM, Esserman LJ, Berry DA. Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1355-1362. doi: 10.1001/jamaoncol.2020.2535.

  PMID: 32701140 BACKGROUND

• Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. doi: 10.1016/S1470-2045(12)70329-7. Epub 2012 Aug 9.

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• Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group investigators. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. doi: 10.1016/S1470-2045(13)70502-3. Epub 2013 Nov 13.

  PMID: 24239210 BACKGROUND

• Semiglazov V, Eiermann W, Zambetti M, Manikhas A, Bozhok A, Lluch A, Tjulandin S, Sabadell MD, Caballero A, Valagussa P, Baselga J, Gianni L. Surgery following neoadjuvant therapy in patients with HER2-positive locally advanced or inflammatory breast cancer participating in the NeOAdjuvant Herceptin (NOAH) study. Eur J Surg Oncol. 2011 Oct;37(10):856-63. doi: 10.1016/j.ejso.2011.07.003. Epub 2011 Aug 16.

  PMID: 21843921 BACKGROUND

• van Ramshorst MS, van Werkhoven E, Mandjes IAM, Schot M, Wesseling J, Vrancken Peeters MTFD, Meerum Terwogt JM, Bos MEM, Oosterkamp HM, Rodenhuis S, Linn SC, Sonke GS. Trastuzumab in combination with weekly paclitaxel and carboplatin as neo-adjuvant treatment for HER2-positive breast cancer: The TRAIN-study. Eur J Cancer. 2017 Mar;74:47-54. doi: 10.1016/j.ejca.2016.12.023. Epub 2017 Feb 10.

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• Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. doi: 10.1016/S1470-2045(11)70336-9. Epub 2011 Dec 6.

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• Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. doi: 10.1001/jamaoncol.2019.3692. Epub 2020 Mar 12.

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• Beitsch P, Whitworth P, Baron P, Rotkis MC, Mislowsky AM, Richards PD, Murray MK, Pellicane JV, Dul CL, Nash CH, Stork-Sloots L, de Snoo F, Untch S, Lee LA. Pertuzumab/Trastuzumab/CT Versus Trastuzumab/CT Therapy for HER2+ Breast Cancer: Results from the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST). Ann Surg Oncol. 2017 Sep;24(9):2539-2546. doi: 10.1245/s10434-017-5863-x. Epub 2017 Apr 26.

  PMID: 28447218 BACKGROUND

MeSH Terms

Interventions

Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Maham Leeza Adil

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: July 5, 2023
• Study Start: June 1, 2023
• Primary Completion: June 15, 2023
• Study Completion: June 18, 2023
• Last Updated: July 5, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)