lapatinib or trastuzumab in combination with an aromatase inhibitor – pro
Several small trials had been reported but this research d not answered the question of whether this triple combination is beneficial.
First – two drug combinations. Three trials were reviewed by Fleeman et al, of the efficacy and safety of lapatinib combined with letrozole (EGF30008) trial, the efficacy and safety of trastuzumab combined with anastrozole(TAnDEM) trial and the efficacy and safety of letrozole combined with trastuzumab (eLEcTRA) trial]. As a result of differences in the exclusion criteria and because one trial was halted prematurely, comparisons across trials were believed to be inappropriate and meta-analysis was not possible. Individually, however, the findings from the trials all suggest that LAP + AI or TRA + AI results in improved progression-free survival and/or time to progression when compared with AIs alone. The trials do not show a statistically significant benefit in terms of overall survival.
On 27 June, 2012, NICE published guidance which did not recommend lapatinib or trastuzumab in combination with an aromatase inhibitor for first-line treatment in postmenopausal women with metastatic hormone-receptor-positive breast cancer that overexpresses HER2. There is an ongoing clinical trial to answer this question, A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer, NCT01160211. Finally, in June 2014, the ALLTO study, a large phase III ALTTO trial disproved the hypothesis that dual anti-HER2 therapy with lapatinib and trastuzumab in the adjuvant setting enhances clinical outcomes in patients with early-stage HER2-positive breast cancer. Disease-free survival (DFS) at 4 years—the primary endpoint—was no better with the two HER2-targeted agents together than with trastuzumab alone.
N Fleeman, A Bagust, A Boland, R Dickson, Y Dundar, M Moonan, J Oyee, M Blundell, H Davis, A Armstrong, and N Thorp Lapatinib and Trastuzumab in Combination with an Aromatase Inhibitor for the First-Line Treatment of Metastatic Hormone Receptor-Positive Breast Cancer which Over-Expresses Human Epidermal Growth Factor 2 (HER2): A Systematic Review and Economic Analysis Health Technology Assessment, No. 15.42
.S. Doss et al, National Institute for Health and Clinical Excellence, MidCity Place, London, UK
http://am.asco.org/altto-trial-findings-raise-questions-approach-drug-development-early-breast-cancer