Purpose: We compared the efficacy and safety of the addition of lapatinib versus trastuzumab, or the combination, to neoadjuvant chemotherapy in HER2-positive breast cancer.

Methods: Potentially eligible trials were identified through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate and toxicity. Pooled relative risks (RR) were estimated for each endpoint with fixed or random effects models, depending on between-studies heterogeneity.

Results: Six trials were identified with 1494 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm than lapatinib plus chemotherapy (RR 1.25, 95% Confidence Interval (CI): 1.08–1.43; p-value = 0.003) (6 trials; 1494 patients). Furthermore, the probability for pCR was significantly higher in the group given both lapatinib and trastuzumab than in the group given trastuzumab alone (RR 1.39, 95% CI: 1.20–1.63; p-value < 0.001) (4 trials; 779 patients). Diarrhea and dermatologic toxicities were statistically more frequent in patients receiving lapatinib than trastuzumab. The combination was associated with a higher rate of diarrhea than trastuzumab alone. No differences were observed regarding cardiac adverse events among patients receiving trastuzumab, lapatinib, or the combination.

Conclusion: These data support the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer in the neoadjuvant setting. The direct comparison of trastuzumab and lapatinib demonstrated that lapatinib is inferior in terms of pCR and toxicity.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-18.