Dual block versus single agent trastuzumab plus chemotherapy as neoadjuvant treatment of HER2-positive breast cancer: a meta-analysis of randomized trials

Date

10 Oct 2016

Session

Poster display

Presenters

Matteo Clavarezza

Citation

Annals of Oncology (2016) 27 (6): 43-67. 10.1093/annonc/mdw364

Authors

M. Clavarezza1, M. Puntoni2, A. Gennari1, L. Paleari1, N. Provinciali1, M. D'Amico1, A. Decensi1

Author affiliations

  • 1 Oncology Unit, Ospedali Galliera, 16128 - Genova/IT
  • 2 Clinical Trial And Biostatistical Unit, Scientific Direction, Ospedali Galliera, 16128 - Genova/IT
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Background

(Neo)adjuvant chemotherapy plus trastuzumab reduces death risk in HER2-positive breast cancer. Randomized trials assessed HER2 dual block in the neoadjuvant setting using pathological complete response (pCR) as the outcome measure. We conducted a meta-analysis of randomized trials testing neoadjuvant dual block versus trastuzumab alone.

Methods

Trials were identified by Medline (PUBMED), ISI Web of Science (Science Citation Index Expanded), Embase, Cochrane library and a reference lists of published studies, review articles, editorials and by hand-searched reports from major cancer meeting reports.

Results

8 randomized trials with 1453 patients were identified, 598 (43.6%) were hormone receptors negative, 774 (56.4%) hormone receptors positive, 832 (57.2%) received taxanes alone and 621 (42.8%) anthracyclines plus taxanes or the docetaxel-carboplatin regimen. Dual block was associated with a significant 14% absolute improvement in pCR rate compared to single agent trastuzumab (Summary Risk Difference SRD 0.14, 95%CI: 0.09 to 0.19). Interaction test by type of chemotherapy was not significant (taxanes-alone: SRD 0.16, 95%CI: 0.10-0.23; polychemotherapy: SRD 0.10, 95%CI: 0.03-0.18; p-interaction 0.298), while it was significant by hormone receptors status (hormone receptors negative: SRD 0.19, 95%CI: 0.12-027; hormone receptors positive: SRD 0.07, 95%CI: 0.01-0.14; p-interaction 0.037). The activity was greater in hormone receptors negative treated with taxanes alone (SRD 0.25, 95%CI: 0.15 to 0.34), compared to hormone receptors positive or hormone receptors negative disease treated with polychemotherapy (SRD 0.08, 95%CI: 0.02 to 0.14; p-interaction 0.012).

Trastuzumab plus Lapatinib (Clin Cancer Res 2016) Trastuzumab plus Lapatinib or Pertuzumab or Neratinib
number of trials 6 8
number of patients 1155 1453
% hormone receptors negative 41.8% 43.6%
% taxane-alone 46.2% 57.2%
ΔpCR overall +13% (95%CI: 0.08-0.19) +14% (95%CI: 0.09-0.19)
p-interaction by type of chemotherapy 0.336 0.298
p-interaction by hormone receptors status 0.157 0.037
p-interaction by taxane-alone and hormone receptors status versus others 0.050 0.012

Conclusions

Based on ΔpCR data, the HER2 dual block plus chemotherapy is a very active treatment only in HER2-positive, hormone receptors negative breast cancer treated with taxane monochemotherapy.

Clinical trial identification

No trial protocol number

Legal entity responsible for the study

E.O. Ospedali Galliera - Genoa

Funding

This meta-analysis was partially supported by AIRC (Associazione Italiana Ricerca Cancro)

Disclosure

All authors have declared no conflicts of interest.

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