ReviewThe efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis

- HER2+ breast cancer is associated with a higher prevalence of brain metastases (BMs).
- Lapatinib (L) is associated with single agent activity toward BMs.
- Lapatinib therapy provided an overall response rate of 30% on BMs in this setting.

IntroductionBreast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs.Material and methodsWe searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and the European Union Clinical Trials Register for studies reporting data on L, singly or in combination with C, for the treatment of HER-2+ BC with BMs. Primary end-points were overall response rate (ORR) and disease control rate (DCR); these were pooled to provide an aggregate value. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Data were pooled using number of events/number of evaluable patients, according to a fixed or random effect model.ResultsOverall, 12 studies were included in the present meta-analysis, for a total of 799 patients with BMs. The pooled overall response rate (ORR) was 21.4% (95% CI 11.7-35.9). After exclusion of patients that received L alone, ORR reached 29.2% (95% CI 18.5-42.7). The pooled median PFS and OS were 4.1 (95% CI 3.1-6.7) and 11.2 (95% CI 8.9-14.1) months, respectively.ConclusionsDue to its activity on BMs, the L + C combination may be considered for HER-2+ BC that has progressed in the brain, when local therapy has been performed or failed and re-irradiation is not feasible.