Abstract P4-22-24: A retrospective study about re-biopsy at disease progression on T-DM1
Authors: Yoshinami T , Hasegawa A , Fujisawa F , Kittaka N , Ishitobi M , Sugimoto N , Nakayama T , Toshinari Y , Tamaki Y , Imamura F 
Published: March 2017

Abstract
Background:
T-DM1 is an antibody-drug conjugate, which consists of trastuzumab, DM1, and linker. It has been established as standard of care for human epidermal receptor (HER) 2-positive metastatic breast cancer (MBC). At the first step, trastuzumab has to combine with extracellular domain of HER2. Then T-DM1 is delivered into HER2-positive cancer cells, and DM1 is released. After that, antitumor activity of DM1 can be exerted. In this way, T-DM1 works on HER2-positive cancer cells with high specificity. This retrospective study is aimed to examine whether HER2 status at disease progression on T-DM1 is related to efficacy of T-DM1.
Patients:
We identiﬁed 23 patients who started treatment with T-DM1 between February 2014 and March 2016 at our department. The data cut-off date was April 30, 2016.
Methods:
We retrospectively reviewed the medical records of these 23 patients and investigated the following items: patient characteristics, time to failure (TTF), objective response, and results of re-biopsy. TTF were analyzed by the Kaplan–Meier method. The definition of HER2-positive was immunohistochemistry 3+, or FISH &gt;2.2.
Results:
There were 23 patients who started administration of T-DM1 for MBC at our department in this period. All patients had HER2-positive MBC which was diagnosed as HER2 positive by examination of samples from primary tumor. At the time of data cut-off, five patients had continued T-DM1 therapy, and 18 patients had finished it due to disease progression in 15 patients and adverse events in three patients. Re-biopsy was conducted to 13 (87%) of 15 patients who experienced disease progression during TDM-1 therapy. Samples of re-biopsy were acquired from the site that showed progression during T-DM-1 therapy. Re-biopsy revealed that HER2 status had changed to negative in six (46%) patients (Negative group), and had remained positive in seven (54%) patients (Positive group). Patient characteristics are shown in table. Median TTF was 65.5 days (95% CI: 34-NA) in Negative group, 126 days (95%CI: 70-140) in Positive group, and 196 days (95%CI: 93-594) in all patients. Proportion of progressive disease (PD) was 83% (five in six patients) in Negative group, 43% (three in seven patients) in Positive group, and 39% (nine of 23 patients) in all patients.
Patient characteristics All patients (23)Negative group (6)Positive group (7)Age at start T-DM1 (year) Median (rang)61 (38-80)63 (48-71)58 (38-78)ECOG PS 0-121 (91%)6 (100%)7 (100%)2-32 (9%)--ER and/or PgR positive13 (57%)5 (83%)4 (57%)ER and PgR negative10 (43%)1 (17%)3 (43%)Number of prior chemotherapy regimens for MBC Median (rang)2 (1-9)2 (1-9)2 (1-5)Prior Lapatinib10 (43%)2 (33%)4 (57%)
Conclusions:
In 46% of patients who received re-biopsy, HER2 status changed to negative. There was a trend that TTF was shorter and PD rate was higher in Negative group than in Positive group. We demonstrated that some of patients who experienced PD during T-DM1 therapy had HER2-negative MBC, and in these patients efficacy of T-DM1 was likely to be insufficient. In such a case that disease progression occurs in a few months of T-DM1 therapy, we have to consider whether its HER2 status remains positive or changes to negative.
Citation Format: Yoshinami T, Hasegawa A, Fujisawa F, Kittaka N, Ishitobi M, Sugimoto N, Nakayama T, Toshinari Y, Tamaki Y, Imamura F. A retrospective study about re-biopsy at disease progression on T-DM1 [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 P4-22-24.