Abstract P4-13-22: Successful targeting HER2 in heavily pretreated HER2-negative metastatic breast cancer patients presenting with elevated serum levels of the HER2 extracellular domain and/or HER2 overexpressing circulating tumor cells

Abstract Background: A considerable proportion of patients (pts) with HER2-negative (HER2-) metastatic breast cancer (MBC) present with elevated serum levels of the soluble HER2 extracellular domain (sHER2) and/or HER2-overexpressing circulating tumor cells (CTCs) during their further clinical course. These "occult" HER2-positive (HER2+) pts may well be candidates for HER2-targeted therapy (Tx) albeit normally not subjected to such treatment. This observational study was undertaken to gain more insights into the feasibility of HER2-directed Tx in occult HER2+ MBC pts in the clinical routine. Methods: A total of 30 pts with heavily pretreated HER2- MBC (ER+, n = 26) showing sHER2 values > 15 ng/mL (n = 8), HER2+ CTCs (n = 7), or both (n = 15) were included. Pts had failed 2-16 prior systemic treatments (median: 7) and did not qualify for recruitment onto a controlled clinical trial. sHER was measured by a chemiluminescence assay (Siemens Helathcare, Eschborn, Germany), CTCs were ennumerated and checked for HER2 expression by using the FDA-cleared CellSearch™ technology (Veridex, Raritan, NJ). All pts received anti-HER2 Tx with trastuzumab (H: n = 18), lapatinib (L: n = 4), H+L (n = 2), or H+pertuzumab (H+P: n = 6). HER2-targeted Tx was given alone (n = 4), or in combination with endocrine agents (n = 7), cytotoxics (n = 17), or other targeted drugs (n = 2). Responses were scored according to RECIST 1.1, OS was calculated from the start of HER2-directed Ctx until death from any reason or loss to follow-up by using Kaplan-Meier statistics. Results: Anti-HER2 Tx was generally well tolerated. Median treatment duration was 16.1 wks (range 1.0-72.9 wks). In 2 pts with L and 1 pt with H+L, Tx was prematurely stopped due to toxicity (diarrhea, fatigue). 2 pts were too early to evaluate (TE). 11 PR, 12 SD, and 5 PD accounted for an objective response rate (ORR) of 36.7% and a clinical benefit rate (CBR) of 76.7%. Median OS was 62.9 wks. In 25 pts, 9 with PR, 12 with SD, and 4 with PD, results of serial sHER2 measurements at baseline and after 3 wks of Tx were available. Most pts with PD showed increasing sHER2 levels. In the majority of pts with PR or SD, sHER2 decreased by more than 20% from baseline. However, 2 pts with PR following L-based Tx showed increasing sHER2 values. In 19 pts, 8 with PR, 7 with SD, and 4 with PD, repeated CTC counts at week 6 from baseline were available. All pts with PD showed increasing CTCs. All pts with SD and PR presented with decreasing CTC counts, most of them normalizing within 6 wks. Conclusions: Our findings indicate that anti-HER2 Tx may be a valid option in pts with heavily pretreated HER2- MBC with pathological sHER2 values and/or HER2+ CTCs in the clinical routine. Thus, determination of both sHER2 and HER2 expression on CTCs appears to be reasonable in tissue HER2-negative MBC pts. Compared to sHER2, serial CTC measurements may be the more accurate predictor of response to anti-HER2 treatment, particularly in pts receiving L as part of their Tx. Results of ongoing randomized trials in this setting are eagerly awaited. Citation Format: Kurbacher CM, Quade A, Eichler C, Kunstmann G, Herz S, Kurbacher JA, Warm MR. Successful targeting HER2 in heavily pretreated HER2-negative metastatic breast cancer patients presenting with elevated serum levels of the HER2 extracellular domain and/or HER2 overexpressing circulating tumor cells. [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 P4-13-22.