Abstract P1-17-02: Ado-trastuzumab emtansine (TDM-1) treatment and brain metastases in HER2 positive metastatic breast cancer patients: Final analysis of an italian multicenter study
Authors: Fabi A , Alesini D , Valle E , Carbognin L , Arpino G , Montemurro F , Ciccarese M , Cannita K , Paris I , Cursano MC , Moscetti L , Ferretti G , De Laurentiis M , Zambelli A , La Verde N , Nisticò C , Gasparro S , Giannarelli D , Cognetti F 
Published: February 2018

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 (Verma et al, NEJM 2012). 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 (Fabi et al, Oncotarget 2017), 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 order to study outcome of disease. MRI was used as assessment imaging.
The number of extracranial metastatic sites in the BM-group and in the nBM-group was 1 for 10 (11.5%) and for 74 patients (34.3%), 2 for 23 (26.4%) and 93 (43%) patients, 3 for 25 (28.7% and 38 (17.6%) and 4 or more for 29 (33%) and 11 (5%), respectively.
In the BM-group, 5 patients (5.7%) had received surgery alone as local treatment for brain metastases, 13 (14.9%) surgery plus stereotactic radio-surgery (SRS), 4 (4.7%) surgery plus whole-brain radiotherapy (WBRT), 23 (26.5%) SRS alone, 40 (45.9%)WBRT alone and 2 (2.3%) 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 (28.2%) and 49 (23.3%) as third line and 33 (38.8%) and 72 (34.3%) 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, 14 (26.4%) partial response and 13 (24.5%) stable disease [brain disease control rate: 54.7%); 24 (45.3%) progressed 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 76% 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.
Citation Format: Fabi A, Alesini D, Valle E, Carbognin L, Arpino G, Montemurro F, Ciccarese M, Cannita K, Paris I, Cursano MC, Moscetti L, Ferretti G, De Laurentiis M, Zambelli A, La Verde N, Nisticò C, Gasparro S, Giannarelli D, Cognetti F. Ado-trastuzumab emtansine (TDM-1) treatment and brain metastases in HER2 positive metastatic breast cancer patients: Final analysis of an italian multicenter study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-02.