Abstract P4-21-11: T-DM1 in HER2 positive advanced breast cancer patients: Real world practice from a multicenter observational study
Authors: Fabi A , De Laurentiis M , Caruso M , Valle E , Moscetti L , Santini D , Cannita K , Carbognin L , Ciccarese M , Rossello R , Arpino G , Leonardi V , Montemurro F , La Verde N , Generali DG , Zambelli A , Scandurra G , Russillo M , Paris I , D'Ottavio AM , Filippelli G , Giampaglia M , Stani S , Fabbri A , Alesini D , Giannarelli D , Cognetti F 
Published: March 2017

Abstract
Background: T-DM1 showed remarkable activity in metastatic HER-2 positive breast cancer (mBC) and it was recently approved for clinical use in patients (pts) who previously failed Trastuzumab- and Taxanes-based therapies. Currently, little is known on the performance of T-DM1 in a “real life” scenario. Therefore, we investigated effectiveness and safety of T-DM1 in Italian daily practice.
Methods: Pts baseline characteristics and clinical outcome of pts with HER-2 positive mBC treated with T-DM1 between 2013 and 2015 at 20 Italian Institutions were retrospectively collected and analyzed.
Results: 300 pts were included in our analysis. Median age was 51 years (27-78); visceral metastases were present in 204 (68%) pts and brain metastases in 86 (29%). It is noteworthy that 111 (37%) pts received T-DM1 as pure second line, 83 (28%) as third line and 96 (32%) as further lines. Moreover 10 (3%) pts had T-DM1 as first line because disease recurrence occurred during or adjuvant trastuzumab of within 6 months of its completion. The overall response rate (ORR) was 40%, global disease control rate (gDCR) 64%, median progression-free survival (PFS) 7.0 months (C.I.95%: 5.6-8.4) and overall survival (OS) at 2 years 63%. Pts with 1, 2 and 3 or more metastatic site had OS at 2 years of 87%, 67% and 46%, respectively (p&lt;0.0001). When T-DM1 was given as second line the PFS was 8.0 months and beyond second-line was 6.8 months. Interestingly, for 38 (13%) pts who progressed after Pertuzumab-plus trastuzumab and taxanes as first line treatment, ORR and gDCR were similar to pertuzumab-naïve patients (38% and 62%, respectively) However PFS was 5.0 months (C.I.95%: 4.3-5.7) compared to 9.0 (95% C.I. 5.5-12.4) achieved in pts not receiving a previous pertuzumab-based treatment. Most frequent grade ≥3 toxicities were thrombocytopenia (2.6%), alopecia (2.1%), hypertransaminasemia (2.2%), neutropenia (1.3%), asthenia (1.3%) and diarrhea (0.4%).
Conclusions: To our knowledge, this is the first real life, multicenter retrospective analysis evaluating efficacy and safety of T-DM1 in pretreated HER-2 positive mBC pts. We observed remarkable results in terms of PFS and OS, especially when T-DM1 was given early in the course of metastatic disease. Shortened PFS in patients progressing after pertuzumab suggest further analyses to better define possible molecular mechanisms of cross-resistences between two molecules. As a whole there was no evidence of significant or unexpected toxicities. Although these findings should be taken with caution due to the retrospective analysis and the different lines of previous treatment considered, we confirmed the potential therapeutic role of T-DM1 across a heterogeneous population of HER-2 positive mBC patients. The final analysis will be presented to the meeting.
Citation Format: Fabi A, De Laurentiis M, Caruso M, Valle E, Moscetti L, Santini D, Cannita K, Carbognin L, Ciccarese M, Rossello R, Arpino G, Leonardi V, Montemurro F, La Verde N, Generali DG, Zambelli A, Scandurra G, Russillo M, Paris I, D'Ottavio AM, Filippelli G, Giampaglia M, Stani S, Fabbri A, Alesini D, Giannarelli D, Cognetti F. T-DM1 in HER2 positive advanced breast cancer patients: Real world practice from a multicenter observational study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-11.