(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.
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.
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%|
|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|
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
This meta-analysis was partially supported by AIRC (Associazione Italiana Ricerca Cancro)
All authors have declared no conflicts of interest.