Abstract P4-12-27: Efficacy and safety of trastuzumab emtansine (T-DM1) vs lapatinib plus capecitabine (XL) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and central nervous system (CNS) metastases: Results from a retrospective exploratory analysis of EMILIA (2013)

Abstract Introduction T-DM1 is an antibody–drug conjugate that was recently approved by the FDA for patients with HER2-positive MBC who have received prior treatment with trastuzumab and a taxane. In the phase 3 EMILIA trial, T-DM1 significantly prolonged progression-free survival (PFS) and overall survival (OS) compared with XL in patients with previously treated HER2-positive MBC (Verma 2012). Because the CNS is a common site of progression in HER2-positive MBC, it is of interest to characterize the incidence of CNS metastases in patients treated with TDM1 vs XL and the efficacy of T-DM1 in patients with pre-existing CNS metastases. Methods EMILIA is a multicenter, randomized, open-label trial in which patients with HER2-positive, unresectable, locally advanced or MBC previously treated with trastuzumab and a taxane were randomized (1:1) to T-DM1 (3.6 mg/kg every 21 days) or XL (X: 1000 mg/m2 bid on days 1–14 of each 21-day cycle; L: 1250 mg/day on days 1–21). Treatment continued until disease progression or unacceptable toxicity. All patients underwent brain magnetic resonance imaging or computed tomography at screening, and follow-up scans were performed as clinically indicated. Those with untreated or symptomatic brain metastases and those who required therapy for symptom control ≤2 months before randomization were excluded from the trial. Patients with CNS metastases at baseline or who developed CNS metastases on study were retrospectively identified using independent review committee data, and exploratory analyses were performed on data from these patients. Results Of the 896 patients without CNS metastases at baseline (T-DM1 = 450; XL = 446), 9 (1.8%) and 3 (0.6%), respectively, developed CNS progression on study. Of the 95 patients with CNS metastases at baseline (T-DM1 = 45; XL = 50), 10 (2.0%) and 8 (1.6%), respectively, developed CNS progression on study. Median PFS in patients with CNS metastases at baseline was 5.9 months in the T-DM1 arm and 5.7 months in the XL arm (HR = 1.000; 95% CI: 0.542–1.844; P = 0.9998). Median OS was 26.8 months and 12.9 months in the T-DM1 and XL arms, respectively (HR = 0.382; CI: 0.184–0.795; P = 0.0081). Multivariate analysis adjusting for baseline risk factors produced similar results. Safety profiles of T-DM1 and XL in patients with CNS metastases at baseline (T-DM1 = 43; XL = 49) were consistent with those for the overall study population. Grade ≥3 adverse events (AEs) were reported in 17 (39.5%) patients in the T-DM1 arm and 29 (59.2%) patients in the XL arm. Serious AEs were reported in 5 (11.6%) and 11 (22.4%) patients in the T-DM1 and XL arms, respectively. No new safety signals were identified. Conclusions In this retrospective exploratory analysis of data from EMILIA, the rate of CNS progression in patients with or without baseline CNS metastases was low in both treatment arms. In the subset of patients with brain metastases at baseline, similar to the intent-to-treat population, T-DM1 was associated with significantly improved OS compared with XL. Prospective phase 3 trials are necessary to confirm these results. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-27.