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 outcome measure. We conducted a meta-analysis 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 ΔpCR 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. ©2016 AACR.

©2016 American Association for Cancer Research.
2016
American Association for Cancer Research.
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