Lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer: a systematic review

Objective: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to cardiotoxicity and increasing resistance associated with trastuzumab, the first-line treatment, there is a need for effective second-line therapies in treating HER2-positive breast cancer. In this context, there has been increasing interest in the combination of lapatinib plus capecitabine. The aim of this systematic review was to assess the efficacy of lapatinib plus capecitabine for HER2-positive breast cancer after progression with trastuzumab therapy, in comparison with capecitabine monotherapy and other agents such as vinorelbine and trastuzumab emtansine.

Materials and methods: We performed a keyword search in five electronic databases (OVID MEDLINE, the Cochrane Library, Web of Science, SCOPUS, and CINAHL; January 2010 to April 2017) for trials in patients with HER2-positive breast cancer that has progressed on trastuzumab. After screening, the relevant studies were assessed for their methodological quality (including selection bias, randomization, control for confounders, and blinding) by two reviewers independently.

Results and discussion: A total of 50 studies were identified; only 6 of those met the inclusion criteria and were analyzed. Five received a weak rating on the quality assessment tool, and none could be considered as being of high scientific quality after taking the risk of bias and other confounding variables into account. The studies demonstrated that lapatinib plus capecitabine is effective in extending median overall (OS) and progression-free survival (PFS) outcomes, achieving OS of 37.6 - 108.7 weeks and PFS of 21.1 - 30 weeks across studies. However, median OS and PFS for trastuzumab emtansine therapy were found to be considerably better (133.9 weeks and 41.6 weeks, respectively) than for lapatinib plus capecitabine.

Conclusion: The results suggest that the combination of lapatinib plus capecitabine can improve PFS and OS in patients with HER2-positive breast cancer that has progressed on trastuzumab. However, it appears that trastuzumab emtansine provides better treatment outcomes in this context.