In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 4_Supplement ( 2016-02-15), p. OT1-02-02-OT1-02-02
Abstract:
Circulating tumor cells (CTCs) are found in patients with primary and metastatic breast cancer (MBC), respectively, and discordance in HER2 and hormone-receptor status between primary tumor, metastases and CTCs is well described. Treatment decisions are still based on the expression profile of solid tumor samples whereas CTCs are thought to cause tumor progression by blood-derived metastases. Nevertheless, targeted therapy based on expression profile of CTCs is not established in clinical routine. Individualized treatment decisions based on presence and phenotype of CTCs will be analyzed within the DETECT study program. Metastatic breast cancer patients with HER2-negative MBC are screened in DETECT III and IV for presence of CTCs by using the CellSearch System (Janssen Diagnostics) which is FDA approved for enumeration of CTCs. Patients are enrolled into the different cohorts according to HER2-phenotype of CTCs. Since February 2012, women with HER2-negative MBC and HER2-positive CTCs are treated in the multicenter randomized Phase III study DETECT III with standard therapy with or without additional HER2-targeted therapy with Lapatinib. For standard therapy, physicians can choose between exemestane, letrozole and anastrozole for endocrine therapy, or docetaxel, paclitaxel, capecitabine, vinorelbine and non-pegylated liposomal doxorubicin for chemotherapy. Efficacy of CTC-based anti-HER2 treatment is evaluated by analyzing CTC-clearance rate after treatment. Patients with only HER2-negative CTCs are recruited for the multicenter open-label phase II study DETECT IV. Since December 2013, women with hormone-receptor positive MBC receive endocrine therapy (tamoxifen, exemestane, letrozole or anastrozole) plus everolimus in DETECT IVa. In February 2015, DETECT IV was extended by the eribulin-cohort which offers a cytotoxic treatment with eribulin for women with triple-negative or hormone-receptor positive, chemotherapy demanding MBC (DETECT IVb). Progression free survival is used for assessment of clinical efficacy with overall survival and disease control rate as secondary objectives. DETECT V, a multicenter open-label phase III study starting in summer 2015, randomizes patients with hormone-receptor positive, HER2-positive MBC to a dual HER2 targeted therapy (Trastuzumab and Pertuzumab) combined with either endocrine therapy or cytotoxic treatment. Quality of life determined by occurrence of adverse events is compared between both treatment arms. For prediction of endocrine treatment response, an "Endocrine Responsiveness Score" is calculated based on expression of estrogen-receptor and HER2 on detected CTCs. More than 1200 patients are already screened in the DETECT study concept. Thus, it is the worldwide largest study concept with therapy decisions resulting from CTC-testing and CTC-phenotypization. The accompanying translational research programs evaluates further markers for molecular characterization of CTCs and prediction of therapy response. Conclusion and Contact The value of CTC phenotypes for making decisions on therapy interventions and predicting treatment responses in patients with MBC is tested in the DETECT study concept. The findings will help to move a step forward towards a more personalized anti-cancer therapy. Citation Format: Schramm A, Friedl TWP, Huober J, Jäger B, Rack B, Trapp E, Fasching PA, Taran F-A, Hartkopf A, Schneeweiss A, Müller V, Aktas B, Pantel K, Meier-Stiegen F, Wimberger P, Kümmel S, Gebauer G, Müller L, Janni W, Fehm T. The DETECT study program – Personalized treatment in metastatic breast cancer based on 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 OT1-02-02.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.SABCS15-OT1-02-02
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
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2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
