Brain metastases and ado-trastuzumab emtansine (TDM-1) treatment in HER2 positive metastatic patients: an Italian multicenter analysis

Abstract

Background: Ado-trastuzumab emtansine (T-DM1) is a drug-antibody conjugate whose activity has been confirmed in HER2+ advanced breast cancer (BC) patients by the phase 3 EMILIA trial. Within the 991 patients enrolled in this trial, about 10% were affected with brain metastases (BM); in this subgroup, safety and efficacy of T-DM1 were confirmed although without any PFS improvement. Patients and methods: In an Italian, multicenter, retrospective analysis involving 303 patients with advanced BC treated with T-DM1, we analyzed 87 patients with BM (BM-group). The study wanted to evaluate the efficacy of T-DM1 on BM; furthermore we compared BM-group with the remaining 216 patients without BM (nBM-group) in terms of outcome disease. MRI was used as assessment imaging. The number of extracranial metastatic sites was 1 for 10 patients (11.5%) in the BM-group and 74 (34.3%) in the nBM-group; 2 for 23 and 93; 3 for 25 and 38; 4 or more for 29 and 11 respectively. In the BM-group, 5 patients (5.7%) had received surgery alone as local treatment for brain metastases, 13 surgery plus stereotactic radio-surgery (SRS), 4 surgery plus whole-brain radiotherapy (WBRT), 23 SRS alone, 40 WBRT alone and 2 WBRT followed by SRS. Twenty-eight patients (32.9%) and 89 (42.4%) in the BM-group and nBM-group, respectively, received T-DM1 as second line, 24 and 49 as third line and 33 and 72 as fourth line. Mean number of cycles was 6 in both groups. Results: Among BM-group, 53 patients (60.9%) were evaluable for response. Two (3.8%) obtained brain complete response (CR), 14 (26.4%) partial response (PR) and 13 (24.5%) stable disease (SD) [brain disease control rate: 54.7%]; 24 progressed (PD) during T-DM1. Regarding extracranial metastases, overall response rate was 35.1% in the BM-group and 38.3% in the nBM-group; 6 months-clinical benefit was 50.6% and 52.3%, respectively. Median PFS was 7 months in the BM-group and 8 months in the nBM-group; when T-DM1 was given as second line, median PFS was 5 months in the BM-group and 11 months in nBM-group (p=0.01) while as third line, in which 60% of patients received lapatinib/capacitabine before TDM1, median PFS was 12 and 13 months (p=NS), respectively. Conclusions: T-DM1 showed a good activity on BM in BC patients. A better outcome was shown in patients previously treated with lapatinib. The identification of clinical and biological prognostic factors could be needed to better select more responder patients with BM to T-DM1.