Eligible studies were randomised controlled trials (RCTs) that compared the two treatments lapatinib plus aromatase inhibitor and trastuzumab plus aromatase inhibitor with each other or each with aromatase inhibitor alone in postmenopausal women receiving first line treatment for metastatic breast cancer. Participants had to be tested HR+ and HER2+ and had not previously received treatment for metastatic disease.
Three trials were included: one of lapatinib plus letrozole compared to letrozole alone (EGF30008); one of trastuzumab plus anastrozole compared to anastrozole (TAnDEM); and one of letrozole plus trastuzumab compared to letrozole alone (eLEcTR). Treatment was administered at the licensed dose until disease progression, at which stage patients received second line therapy. There were differences between the studies in the second line treatment received; in EGF30008 a much greater proportion of patients received second-line chemotherapy than in the other trials and patients were excluded if they had extensive symptomatic visceral disease and/or disease that was rapidly progressing or life-threatening.
All trials included patients who were HR+/HER2+. Two trials (EGF30008 and eLEcTRA) also included patients who were HR+/HER2 negative. Outcomes of interest included overall survival, progression-free survival, time to progression, response rate, adverse effects, clinical benefit rate and health-related quality of life (HRQoL).
Two reviewers independently selected studies for inclusion. Any discrepancies were resolved by consensus.