Department for Obstetrics and Gynecology Hanover Medical School Carl-Neuberg-Str. 1 30625 Hanover, Germany A prospective multicenter real-world study on neoadjuvant treatment and clinical outcome in TNBC patients Kuehnle E1, Kaur P1, Siggelkow W2, Luebbe K2, Schrader I2,7, Noeding S3, Noeding KH4, Noesselt T5, Arfsten M6, Busch C5, Uleer C8, Krentel N1, Hillemanns P1, Dörk T1, Park-Simon TW1

1 Department of Obstetrics and Gynecology, Breast Center, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hanover, Germany 5 Sana Klinikum Hameln-Pyrmont, Breast Center, Saint-Maur-Platz 1, 31785 Hameln, Germany 2 DIAKOVERE Henriettenstift, Breast Center, Schwemannstraßee 17, 30559 Hanover, Germany 6 Kreiskrankenhaus Stadthagen, Breast Center Schaumburg, Am Krankenhaus 1, 31655 Stadthagen, Germany 3 Klinikum Hannover Nordstadt, Cooperative Breast Center Klinikum Region Hanover, Herrenhäuser Kirchweg 5, 30167 Hanover, Germany 7 Gynäkoonkologische Praxis am Pelikan Platz Hannover, Germany 4 HELIOS Klinikum Hildesheim, Breast Center, Senator-Braun-Allee 33, 31135 Hildesheim, Germany 8 Frauenärzte am Bahnhofsplatz, Bahnhofsplatz 5, 31134 Hildesheim, Germany

Introduction Results 120.0% Chemotherapy Treatment N (%) Controversy exists with regards to 157/227 patients (69%) received regime dose <80%

100.0% 96.6% Taxan 4 0 0% the optimal regimen for NACT and 70/227 patients (31%) 94.7% neoadjuvant chemotherapy adjuvant chemotherapy. 69/157 Taxan/Platin 14 2 14% 80.0% TAC 28 1 4% 80.0% 75.4% (NACT) of TNBC. Platinum-based (44%) patients achieved pCR EC-Pac/Doc 97 8 8% 66.2% 66.7% regimens seem to be more active (Breast+Axilla). 26/69 (38%) ETC 30 2 7% 60.0% EC-Pac 23 4 17% in TNBC improving pCR rates received platinum-based NACT. In (Alliance-like) significantly. But adding platinum 85 patients pCR was not P=0.007 P=0.001 40.0% FEC-Doc 2 0 0% 33.8% 33.3% to an anthracycline/taxane achieved. 15/85 (18%) patients Antracyclin+Taxan 5 1 20% 24.6% 20.0% Pac+Myocet+Carb 13 1 8% pCR pCR chemotherapy regime comes at received platinum and 70/85 20.0% o (GeparSixto) No pCR No pCR

the expense of greater toxicity. Its (82%) non-platinum-based NACT. 5.3% 3.4% TC 7 0 0 impact on survival and long-term- The proportion of platinum-based 0.0% Platin yes 51 8 16% Platinum No Platinum Platin No 176 13 7% outcomes remains undetermined. NACT increased from 2014 (Fig. 2011 2012 2013 2014 2015 2016 In this real-world multicenter study 1). pCR was significantly higher neoadjuvant regimens, pCR rates among patients with platinum- and survival were evaluated. based chemotherapy (chi-square, Fig. 1 Implementation of platinum-based chemotherapy 2011-2016 Tab 1. Toxicity of different chemotherapy regimes Fig. 3 OS as a function of pCR Fig. 4 DFS as a function of pCR p < 0.005) (Fig. 2). Dose reduction Material and methods < 80% was seen in 8/51 (16%) 70.0% Conclusion which pCR rates of 60% (CALBG NACT the benefit of adding 61.4% 60.5% This prospective real-world study patients receiving platinum-based 60.0% Our trial confirms that platinum 40603) and 53% (GeparSixto platinum is questionable. In based NACT can achieve GBG66) were achieved. However, contrast, the addition of platinum was conducted from 2012-2017 in chemotherapy vs 13/176 (7%) in 50.0% significantly higher rates of pCR in in our trial 16% of the patients seems appropriate in those six certified breast cancer centers non-platinum-based 40.0% 37.7% in the region of Hanover, chemotherapy. Mean follow up 34.6% patients with TNBC. pCR was discontinued treatment due to patients with higher stage cancer 30.0% Germany, by using a personal was 18.5 months (1-70months). associated with significantly longer toxicity. Therefore these protocols (stage II/III) and those who show questionnaire and data from the Preliminary data shows a 20.0% DFS and OS. The Alliance protocol should be used in carefully only limited response to NACT. (CALBG 40603) was the preferred selected patients. In daily care medical records. All patients with significant difference in OS 10.0% choice of treatment regimen close monitoring of treatment primary TNBC (ER<1%, PR<1%, (p=0.007) (Fig.3) and DFS 0.0% Her2/neu 0, 1+ or 2+ FISH/CISH (p=0.001) (Fig. 4) for patients with pCR No pCR pCR No pCR followed by the GeparSixto response is essential during NACT. No platinum Platinum negative) were eligible. a pCR. protocol. In our study the pCR rate In patients who have a rapid Fig. 2 pCR with or without platinum was below that of both trials in clinical response to platinum-free

Hanover Medical School, Department of Obstetrics and Gynecology, Carl-Neuberg-Straße 1, 30625 Hannover, Germany, [email protected], www.mh-hannover.de