Purpose: (Neo)adjuvant treatment with chemotherapy plus trastuzumab reduces recurrence and death risk in HER2-positive breast cancer. Randomized trials assessed HER2 dual block by adding lapatinib to trastuzumab and chemotherapy 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 with lapatinib and trastuzumab versus trastuzumab alone in HER2-positive breast cancer. Experimental design: 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: Six randomized trials including 1155 patients were identified, of whom 483 (41.8%) were hormone receptors negative, 672 (58.2%) hormone receptors positive, 534 (46.2%) received taxanes alone and 621 (53.8%) anthracyclines plus taxanes or the docetaxel-carboplatin regimen. Overall, the dual block was associated with a significant 13% absolute improvement in pCR rate compared to single agent trastuzumab (Summary Risk Difference, SRD 0.13; 95%CI: 0.08 to 0.19). The activity was greater in hormone receptors negative patients who received chemotherapy with taxanes alone (SRD 0.25; 95%CI: 0.13 to 0.37), compared to hormone receptors positive or hormone receptors negative disease treated with anthracyclines plus taxanes or the docetaxel-carboplatin regimen (SRD 0.09; 95%CI: 0.02 to 0.15; p-interaction 0.05). Conclusions: Based on ∆pCR data, the dual block with trastuzumab and lapatinib plus chemotherapy is a very active treatment only in HER2-positive and hormone receptors negative breast cancer treated with taxane monochemotherapy.
- Received August 6, 2015.
- Revision received April 11, 2016.
- Accepted April 14, 2016.
- Copyright ©2016, American Association for Cancer Research.