This systematic review conducted by researchers with the NHS Health Technology Assessment (HTA) programme examined the clinical- and cost-effectiveness of lapatinib (LAP) in combination with an aromatase inhibitor (AI) and trastuzumab (TRA) in combination with an AI for the first-line treatment of patients who have hormone receptor-positive (HR+)/human epidermal growth factor 2-positive (HER2+) metastatic breast cancer.

A search for literature was conducted until May 2010 and three trials were included in the systematic review:

1. lapatinib combined with letrozole (EGF30008 trial)
2. trastuzumab combined with anastrozole (TAnDEM trial)
3. letrozole combined with trastuzumab (eLEcTRA trial)

Due to differences in the exclusion criteria and because one trial was halted prematurely, comparisons across trials were not considered appropriate and meta-analysis was not possible. Individually, however, the findings from the trials indicated the following:

• LAP + AI or TRA + AI results in improved progression-free survival and/or time to progression when compared with AIs alone.

• There was no statistically significant benefit in terms of overall survival.

Two separate economic analyses based on the completed trials found that neither LAP + AI nor TRA + AI was cost-effective when compared with AI monotherapy.

This review concluded from these data that “LAP + AI and TRA + AI appear to be clinically more effective than AI monotherapy, but neither is cost-effective compared with AIs alone. It was not possible to compare LAP + AI with TRA + AI. Future research should include research into treating mBC in the HR+/HER2+ population who are not TRA (or LAP) naive and into comparing the clinical effectiveness of AIs as monotherapy in patients with HER2+ and human epidermal growth factor 2-negative breast cancer.”