eLEcTRA trial: Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first line treatment in patients with hormone-receptor-positive, HER2-positive metastatic breast cancer (MBC)

BACKGROUND: Letrozole (LET) and trastuzumab (TRA) are well established for the treatment of hormone-receptor (HR) positive metastatic breast cancer (MBC) patients and HER2 positive disease, respectively. The “eLEcTRA” trial was designed to compare the efficacy and safety of LET combined with TRA to LET alone in patients that are both HER2 and HR positive. Furthermore, LET alone was compared in patients with HER2 and HR positive disease vs. those with HER2 negative, HR positive tumors. METHODS: In this multicenter trial, 92 patients from 32 sites in 7 countries were enrolled from 2003 to 2007. The majority of these patients (57) were recruited from 14 German sites. Patients with HER2 and HR positive MBC were randomized to either LET alone (Arm A, n = 31) or LET + TRA (Arm B, n = 26) as first-line treatment. In addition, 35 patients with HER2 negative and HR positive tumors were assigned to receive LET alone as first-line treatment (Arm C). Tumor response assessments were based on RECIST. Primary endpoint was time to progression (TTP), secondary endpoints were overall response rate (ORR) and clinical benefit rate (CBR). RESULTS: Median age in the three arms was 61 (arm A), 61,5 (arm B), and 70 years (arm C), respectively. Median TTP in the LET alone arm (A) was 3.3 months compared to 14.1 months in the LET + TRA combination arm (B) (hazard ratio = 0.67; p = 0.23) and 15.2 months in arm C (hazard ratio = 0.71; p = 0.03). CBR was 39% for arm A compared to 65% in arm B (odds ratio 2.99, CI 1.01–8.84) and 77% in arm C (odds ratio 5.34, CI 1.83–15.58), respectively. ORRs were 13% for arm A, 27% for arm B, and 11% for arm C. LVEF as cardiac safety parameter showed no change from baseline to the minimum value during the treatment for arms A and C and a slight decrease by 5% for arm B. The incidence of other cardiac adverse events was comparable in all arms (10%, 8%, and 9%). GI disorders or musculoskeletal and connective tissue disorders were slightly more frequent for patients receiving LET and TRA (arm B). CONCLUSION: The results of the eLEcTRA trial show that the combination of LET and TRA is superior to LET alone as first-line therapy in patients with HER2 and HR positive MBC and that the combination can be safely administered. Our results also confirm earlier evidence that aromatase-inhibitor therapy alone is only associated with a rather short TTP in HER2 and HR positive MBC. Interestingly, outcome in LET-treated patients with HER2 negative, HR positive tumors is significantly better compared to that associated with tumors with both HR and HER2 expression.