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

Purpose: (Neo)adjuvant treatment with chemotherapy plus trastuzumab reduces recurrence and death risk in HER2-positive (HER2+) breast cancer. Randomized trials assessed HER2 dual block by adding lapatinib to trastuzumab and chemotherapy in the neoadjuvant setting using pathologic complete response (PCR) as the outcomemeasure.We conducted ametaanalysis of randomized trials testing neoadjuvant dual block with lapatinib and trastuzumab versus trastuzumab alone in HER2+ breast cancer. Experimental Design: Trials were identified by Medline (PubMed), ISI Web of Science (Science Citation Index Expanded), Embase, Cochrane library, and reference lists of published studies, review articles, editorials, and by hand-searched reports from major cancer meeting reports. Results: Six randomized trials including 1,155 patients were identified, of whom 483 (41.8%) were hormone receptor-negative, 672 (58.2%) hormone receptor-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 with single-agent trastuzumab (summary risk difference, SRD 0.13; 95% CI, 0.08-0.19). The activity was greater in hormone receptor-negative patients who received chemotherapy with taxanes alone (SRD 0.25; 95% CI, 0.13-0.37), compared to hormone receptor-positive or hormone receptor-negative disease treated with anthracyclines plus taxanes or the docetaxel-carboplatin regimen (SRD 0.09; 95% CI, 0.02-0.15; Pinteraction = 0.05). Conclusions: On the basis of DPCR data, the dual block with trastuzumab and lapatinib plus chemotherapy is a very active treatment only in HER2+ and hormone receptor-negative breast cancer treated with taxane monochemotherapy. Clin Cancer Res; 22(18); 4594-603.