Abstract P3-13-07: Does treatment response to new agents differ between visceral and non-visceral metastatic breast cancer: A systematic literature review of registration trials

Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (mBC) is an important consideration for their subsequent use in clinical practice. Unfortunately, such subgroup analyses are often exploratory, rarely statistically adequately powered and may thus be misleading. In a systematic literature review, we evaluated differences in outcome (taking into account the diversity of available study data, inhomogeneous in- and exclusion criteria and subgroup-analyses) regarding progression free survival (PFS), time to progression (TTP), overall survival (OS) and visceral versus non-visceral disease. The impact of HER2- and hormone receptor-status was also considered. Methods: A systematic literature search (6362 hits) in the meta-Database PubMed (U.S. National Library of Medicine) was performed for the last 20 years. 257 studies (n=126.291) were included for further analysis. 69 studies had published data for visceral (i.e. presence of visceral metastases independent of the presence of other metastasis sites) vs. non-visceral (i.e. non-visceral metastases in the absence of visceral involvement) disease including phase III trials plus studies that had further used their data. Out of these 69 studies we selected n=16 studies (n=13.083) by considering (A) the information given in the medical product's professional information and (B) the decision of the U.S. Food and Drug Administration or the European Medicine Agency for the approval of the respective therapeutic agents which are now used in treatment of mBC. All selected 16 studies had looked at the endpoints mentioned above. In order to achieve comparability, we extracted the information of hazard ratios (HR), confidence intervals (CI) and times in weeks (if available) for PFS, TTP, OS of the entire study population, which was divided into three groups: HER2-positive, HER2-negative, unknown HER2 status. Results: No statistically significant difference in treatment response was found in mBC patients with visceral vs. non-visceral metastasis looking at HRs and CIs. Relevant, yet not statistically significant differences were found in the specific response of visceral metastases to modern combination therapies, especially in HER2-positive breast cancer: There was an increased benefit regarding OS using Lapatinib combined with Trastuzumab or Trastuzumab and Docetaxel combined with Pertuzumab. Additionally, in two chemotherapy trials, there was a numerical difference between therapy response in visceral vs. non-visceral metastases regarding PFS in the unknown HER2 group, and regarding OS in the HER2-negative group. Conclusions: Using a systemic literature search, we stratified published studies of the last 20 years considering HER2 and hormone receptor status with respect to metastasis pattern. In the subgroup analyses, we did not find any significant differences in response rates for visceral vs. non-visceral metastasis. For targeted therapies based on a biomarker, there seems to be a beneficial effect of combination therapies regarding OS in visceral disease. At the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in mBC. Citation Format: Rachel Würstlein, Maximilian Bardenhewer, Alexander König, Thomas Kolben, Caroline Gehring, Nadia Harbeck. Does treatment response to new agents differ between visceral and non-visceral metastatic breast cancer: A systematic literature review of registration trials [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-13-07.