Abstract P4-13-28: Identification of patients (pts) at high risk for early death with advanced or metastatic breast cancer (MBC), not receiving salvage treatment after 1st-line (1stL) therapy with trastuzumab (T) – Results of a prospective national non-interventional study (NIS) in Germany
Authors: Jackisch C , Schoenegg W , Reichert D , Welslau M , Selbach J , Harich H-D , Tesch H , Keitel S , Hinke A 
Published: May 2016

Abstract
Background: The advent of T as targeted agent has markedly improved survival in pts with HER2-positive (HER2+) MBC. Standard of care is the permanent inhibition of the HER2neu pathway. It would be beneficial to identify patients with an early unfavorable course of the disease upfront, who might benefit from continuous anti-HER2 treatment, since more effective HER2-targeted agents are available.
Patients and methods: We recruited 1843 pts with HER2+ MBC from 2000-2010 in a national prospective NIS in Germany. 1042 pts received T as part of their 1st-L combination therapy either with chemotherapy (CT) and/or endocrine therapy (ET) for MBC. At that time, treatment beyond progression with T was the only available treatment option as 2nd-L anti-HER2 treatment. HER2-positivity (IHC3+ or IHC2+ and FISH+) was assessed according to standard procedures. Detailed information on study treatment and course of disease was collected for at least 1 y (year). Thereafter, long-term outcome data were retrieved up to 11 y.
Results: 153 pts were selected as, presumably, "high risk" cohort (C1). C1 was defined by either early death reported without any formal detection of progressive disease (PD) (C1a; n = 94), or death occurring within 3 months (mth) after PD, without any salvage therapy given (C1b; n = 59). A second cohort was defined by at least one documented salvage treatment after PD under 1st-L T therapy (C2; n = 365). In C2, 2nd-, 3rd-, 4th-, 5th- and 6th-L therapy were reported in 70%, 46%, 27%, 15%, and 7% of pts. Median overall survival (OS) in C1 vs. C2 was 14.4 (95% confidence interval: 12.0 - 18.2) vs. 45.0 mth (41.2 – 53.4). 3 y-survival was 11% in C1, compared to 65% in C2. Median time to progression in C2 was 11.8 mth (10.9 – 13.0). A correlation with treatment intensity could be ruled out as, on the contrary, less pts in C1 received ET ± T only (11% vs. 17%) and taxane treatment was more frequent in the high risk population (59% vs. 45%).
Compared to C2 pts, C1 pts are characterized by an older median age (63.4 vs. 58.4 y) and higher number of elderly pts, defined as &gt; 70 y (26 vs. 11%; p&lt;0.0001). In addition, negative estrogen receptor status (ER-) was more frequent in C1 than in C2 (41 vs. 28%, p=0.0038), as were hepatic lesions (50 vs. 41%, p=0.070), the number of metastatic sites (p=0.015), and a poorer ECOG status (p&lt;0.0001). No major differences between the two cohorts were detected with respect to tumor grading, stage IV at presentation, adjuvant therapy, relapse-free interval as well as metastatic lesions confined to the bones and lungs.
Conclusions: Based on our findings, pts displaying the characteristics age &gt; 70 y, ER-, high metastatic load, and poor ECOG status are less likely to receive 2nd-L therapy due to the high risk for early PD or death. About 30% of pts with HER2+ tumors go off treatment with each step of further-line therapy. This implicates that treatment including a permanent blockade of the HER2neu pathway implementing the available new compounds in this field should be considered even in the subset of pts at high risk for relapse.
Citation Format: Jackisch C, Schoenegg W, Reichert D, Welslau M, Selbach J, Harich H-D, Tesch H, Keitel S, Hinke A. Identification of patients (pts) at high risk for early death with advanced or metastatic breast cancer (MBC), not receiving salvage treatment after 1st-line (1stL) therapy with trastuzumab (T) – Results of a prospective national non-interventional study (NIS) in Germany. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-28.