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Introduction/Background* The accelerated US Food and Drug Administration approval of pembrolizumab validated the efficacy of anti-PD-(L)1 therapy for patients with recurrent/metastatic cervical cancer; however, the objective response rate (ORR) with pembrolizumab was 14.3% in patients with PD-L1–expressing tumours. Human papillomavirus infection is implicated in >95% of cervical cancers and is linked to upregulation of TGF-β signalling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 monoclonal antibody blocking PD-L1. We report pooled safety and efficacy in patients with pretreated, immune checkpoint inhibitor-naive, recurrent/metastatic cervical cancer treated with bintrafusp alfa in phase 1 (INTR@PID 001; NCT02517398) and phase 2 (study 012; NCT03427411) studies. Methodology Patients received bintrafusp alfa 0.3-30 mg/kg (phase 1 dose escalation) or 1200 mg every 2 weeks (phase 1 dose expansion and phase 2) until progressive disease, unacceptable toxicity, or withdrawal. Treatment past progression was allowed. Primary endpoints were safety (phase 1 dose escalation) and best overall response per RECIST 1.1 (phase 1 dose expansion and phase 2). Result(s)* As of May 15, 2020 (phase 1) and December 22, 2020 (phase 2), 39 patients had received bintrafusp alfa for a median duration of 2.8 months (range, 0.5-19.3). The median follow-up to data cutoff was 35.0 months and 24.1 months for the phase 1 and phase 2 studies, respectively. All patients had received prior anticancer therapy; 16 (41.0%) had received ≥3 regimens. Confirmed ORR was 28.2% (table 1); responses occurred irrespective of Moore criteria (phase 1), tumour histology, prior bevacizumab treatment, or radiation treatment. Median overall survival was 13.4 months. No new safety signals and no treatment-related deaths were observed; side effects were manageable. Conclusion* Bintrafusp alfa had a manageable safety profile and demonstrated clinical activity in patients with heavily pretreated, immune checkpoint inhibitor-naive recurrent/metastatic cervical cancer. © 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.

Introduction Controversy exists with regards to the optimal regimen for neoadjuvant chemotherapy (NAC) of TNBC. Platinum-based regimens seem to be more active in TNBC improving pCR rates significantly. But adding platinum to an anthracycline/taxane chemotherapy regime comes at the expense of greater toxicity. Its impact on survival and long-term-outcomes remains undetermined. Practical guidelines vary across leading international professional societies. In this real-world multicenter study neoadjuvant regimens, pCR rates and survival were evaluated. Material and methods This study was conducted from 2012-2017 in six certified breast cancer centers in the region of Hanover, Germany, including rural and urban populations by using a personal questionnaire and data from the medical records. All patients with primary TNBC (ER Results 143/217 patients (66%) received NAC and 74/217patients (34%) adjuvant chemotherapy. 63/143 (44%) patients achieved pCR. 23/63 (35%) received platinum-based NAC and 40/63 (65%) received chemotherapy without platinum. In 80 patients pCR was not achieved. 12/80 patients received platinum and 68/80 non platinum-based NAC. pCR was significantly higher among patients with platinum-based chemotherapy (chi-square, p < 0.003). 20/23 patients who achieved pCR received NAC containing anthracycline/taxane/carboplatin, 3/23 patients received a taxane/carboplatin-based regime. Treatment discontinuation was seen in 12/35 (34%) patients receiving platinum-based NAC vs 15/108 (14%) in non-platinum-based NAC. Mean follow up was 17 months (1-70months). A significant difference in OS (p=0.007) and DFS (p=0.001) was seen for patients with a pCR. Conclusion Our trial confirms that platinum based NAC achieves significantly higher rates of pCR in patients with TNBC. pCR was associated with significantly longer DFS and OS. The CALBG protocol (CALBG 40603) was the preferred choice of treatment regimen followed by the GeparSixto protocol. In our study the pCR rate was comparable to that of both trials in which pCR rates of 60% (CALBG 40603) and 53% (GeparSixto) were achieved. However, in our trial 34% of the patients discontinued treatment due to toxicity. Therefore these protocols should be used in carefully selected patients. In a real world setting less toxic chemotherapy regimens achieved a pCR rate of 37%. In terms of toxicity and adherence to chemotherapy, these regimens are reasonable alternative options. In daily care close monitoring of treatment response is essential during NAC. In patients who have a rapid clinical response to platinum-free NAC the benefit of adding platinum is questionable. In contrast, the addition of platinum seems to be appropriate in those patients who show only limited response under NAC. Citation Format: Kuehnle E, Kaur P, Siggelkow W, Luebbe K, Schrader I, Uleer C, Noeding S, Noeding K-H, Noesselt T, Arfsten M, Busch C, Krentel N, Hillemanns P, Dörk T, Park-Simon T-W. A prospective multicenter real-world study on neoadjuvant treatment and clinical outcome in TNBC patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-10.

Introduction/Background Globally, cervical cancer is one of the most common and lethal gynaecological cancers. Advanced/metastatic disease is typically treated with chemotherapy, often with poor objective response rates (ORRs) and durations of response (DORs) in pretreated patients; ORRs with anti-PD-1 therapies range from 12%-26%. Bintrafusp alfa* (M7824) is an innovative first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking PD-L1. We report safety and efficacy in patients with cervical cancer treated with bintrafusp alfa in dose-escalation and expansion phases of an ongoing phase 1 trial (NCT02517398). Methodology Patients with advanced/metastatic disease received bintrafusp alfa 0.3–30 mg/kg (dose-escalation, n=10) or 1200 mg (expansion, n=15) Q2W until PD, unacceptable toxicity, or withdrawal. Treatment past PD was allowed if adverse events (AEs) were tolerable and no new treatment was indicated. Primary endpoints were safety (dose-escalation) and BOR (expansion). Results As of 9 January 2019, 25 patients were treated for a median duration of 9.6 (range, 2.0–72.0) weeks. Six patients had confirmed responses per RECIST 1.1 (ORR, 24.0%); 5/6 responses were ongoing at data cutoff (median DOR not reached; range, 2.3±24.9+ months). One additional patient had a delayed PR that was ongoing for 8.7 months at data cutoff, with 73.3% disease shrinkage after initial PD (total clinical response rate, 28.0%). Responses occurred irrespective of PD-L1 protein expression: 1 patient with PD-L1-negative disease had a response. Grade 3 treatment-related AEs (TRAEs) occurred in 6 patients (24.0%); 1 patient experienced a grade 4 TRAE (4.0%; hypokalaemia). Six patients discontinued treatment due to TRAEs. No treatment-related deaths occurred. Conclusion Bintrafusp alfa has a manageable safety profile and promising clinical activity with durable responses. Further investigation of bintrafusp alfa in cervical and other HPV-associated cancers is ongoing (NCT03427411). Updated results will be presented. Disclosure TL discloses honoraria from Foundation Medicine, Takeda, and PUMA, and receives grant/research support from Foundation Medicine, Pfizer, AstraZeneca, Hengrui, and Eureka. JS discloses inventorship on a National Institutes of Health patent related to the work. LSO and ID disclose employment with EMD Serono, Inc. CH discloses employment with Merck Healthcare KGaA. JLG discloses that National Cancer Institute has a cooperative research and development agreement with EMD Serono, Inc. and discloses inventorship on a National Institutes of Health patent related to the work. All remaining authors have nothing to disclose. Funding for this trial was provided in part by the Center for Cancer Research, National Cancer Institute, and National Institutes of Health Clinical Center. This trial was sponsored by Merck Healthcare KGaA, Darmstadt, Germany, and is part of an alliance between Merck Healthcare KGaA and GlaxoSmithKline. *Proposed INN

Introduction Although the health of immigrants is an important issue in national health care policy there is a serious shortage of data in many countries. Most studies lack information on educational status which is a major limitation. In this prospective cross-sectional-study we analyzed the influence of immigration background and educational status on the participation in mammography screening programs in Lower-Saxony, Germany. Material and methods Data collection was conducted from 2012-2016 in six certified breast cancer centers using a personal questionnaire and data from the patients' medical records. Stratification into subgroups was carried out according to first and second generation immigrants and country of origin. Results 1547/2129 primary breast cancer cases were analyzed. The percentage of patients with a history of immigration in our study cohort was 17.7%. The majority of them were citizens of EU27 Member states. First generation immigrants (n= 146), second generation immigrants (n=129), natives (n= 1272). No significant difference was seen in sex, age, tumor stage, histology, grading, Ki-67, Her2/neu-status, and hormone receptor status. A 100% participation rate in the mammography screening program was seen in patients with no school graduation. The lowest participation rate (85.5%) was seen in the group of native Germans with a college graduation and in first generation immigrants with a high school graduation (86.7%). Detailed statistical analysis will be presented on the poster. Conclusion No difference was seen between immigrants and native Germans with regard to tumor biology. In first-generation immigrants mammography screening was well accepted despite cultural and linguistic differences. Participation rate decreased with higher education level in all groups. High school graduates with immigrant background participated more frequently in breast cancer screening than native high school graduates. These findings mainly relate to immigrants from EU27 Member states rather than immigrants from non EU countries. Citation Format: Kuehnle E, Oeztuerk T, Siggelkow W, Luebbe K, Moser A, Noeding S, John J, Noesselt T, Busch C, Arfsten M, Lemster S, Hillemans P, Doerk T, Park-Simon T-W. Prospective cross-sectional-study on participation in mammography screening according to immigration background and education status [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-10-09.

Background: Inhibition of HER2 and HER3 heterodimerisation is a novel treatment concept in HER2-”low” expressing breast cancer (BC). Lumretuzumab, a glycoengineered monoclonal anti-HER3 antibody, in combination with pertuzumab has demonstrated synergistic anti-tumor activity in preclinical HER2–low expressing preclinical BC models. Methods: This open-label, multicenter phase I study selectively enrolled metastatic BC patients (pts) expressing HER3 protein and low levels of HER2 (defined as IHC 1+ and 2+ and ISH-negative) in a formalin-fixed paraffin-embedded pretreatment tumor biopsy sample. Eligible pts were treated with a combination of paclitaxel (PA) qw plus lumretuzumab (L) and pertuzumab (P) q3w in three dose cohorts. The safety, antitumor activity and tumor biomarkers including protein expression (IHC, MS) and mutational data (NGS) in association with clinical activity were evaluated. Results: Overall, 35 pts were included in this study. The median age was 60 (range: 33 to 77) years. The median number of prior treatments for metastatic disease ranged from 0 to 5 with 23 pts (65.7%) without prior chemotherapy for metastatic disease. Cohort 1 was treated with PA at 80 mg/m2, L at 1000 mg and P at 840 mg for Cycle 1 followed by 420 mg for the following cycles. This cohort was stopped after two pts both experienced grade 3 diarrhea within the first treatment cycle which was considered a dose-limiting toxicity (DLT). For Cohort 2 the dose of L was reduced to 500 mg based on PK modelling and simulation data. No DLTs were seen for the first 6 pts. A total of 20 pts were recruited with an objective response rate (ORR) and disease control rate (DCR) of 30% and 75%, respectively, and 56% and 78%, respectively, for 1st-line pts (n=9) in this cohort. Diarrhea (≥G3) and hypokalemia (≥G3) occurred in 50% and 55% of pts, respectively, and all pts experienced chronic diarrhea throughout the course of treatment. For Cohort 3 the dose of L was maintained at 500 mg, PA at 80 mg/m2, and P was administered at 420 mg at all cycles. In addition, a prophylactic loperamide regimen was introduced. Altogether, 13 pts - all 1st-line for metastatic disease - were treated. No DLTs were seen for the first 6 pts. Diarrhea (≥G3) and hypokalemia (≥G3) were reduced to 31% and 15%, respectively, but chronic diarrhea was still observed throughout the treatment in all pts. The ORR and DCR were 31% and 77%, respectively. Preliminary mechanistic safety experiments revealed HER2/HER3-dependent chloride channels in the intestine as likely cause of diarrhea. Biomarker data will be presented along with updated clinical and safety data. Conclusions: The combination of L, P and PA was associated with high rates of persistent diarrhea. Dose modifications and prophylactic anti-diarrheal medication led to significantly reduced diarrhea intensity but did not change the incidence and persistence of diarrhea overall. Despite encouraging clinical activity especially in 1st line pts, the therapeutic window of this combination is too low to warrant further clinical development. Citation Format: Schneeweiss A, Park-Simon T-W, Albanell J, Lassen U, Cortes J, Dieras V, May M, Schindler C, Marmé F, Cejalvo JM, Martinez-Garcia M, Gonzalez I, Lopez-Martin J, Welt A, Joly F, Michielin F, Jacob W, Adessi C, Moisan A, Meneses-Lorente G, James I, Ceppi M, Hasmann M, Weisser M, Cervantes A. Phase Ib study evaluating the safety and clinical activity of lumretuzumab combined with pertuzumab and paclitaxel in HER2-low metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-13.

Background: The incidence of brain metastases (BM) in breast cancer patients is rising and has become a major clinical challenge. So far, limited therapeutic options and insights into the biology of BM exist since only a few studies analyzed exclusively data of breast cancer patients. In order to improve this situation, our multicenter registry was initiated in 2014: Brain Metastases in Breast Cancer Network Germany (BMBC, GBG79). Materials and Methods: Patients with BM diagnosed since 2000, a history of breast cancer and no history of other malignant or neurologic disease can be included. Registration is allowed retrospectively as well as prospectively into a web–based database ("MedCodes"). Characteristics of the primary tumor, metastatic disease and BM as well as treatment details are documented. For this first analysis, 548 patients from 39 German centers were included. Results: Median age at first diagnosis of BM was 55 years (25 – 90 years). 43% of patients (233/548) were HER2 positive, 19% (n=105) were triple–negative and 25% (n= 138) had luminal primary tumors indicating a selection of patients with specific tumor biology who develop BM. 54 % of the patients (n=267) had up to three BM whereas 45% (n=223) had more than three BM. 19% of patients (n=106) had BM without evidence of extracranial disease. 27% of the patients (n=146) underwent surgery of the BM. Of these patients, 61% (n= 89) were treated with whole brain radiotherapy and 16% (n=23) with stereotactic radiotherapy. In patients without surgery (n=397), 73% (n=289) received whole brain radiotherapy and 7% (n=28) stereotactic radiotherapy. Median time from diagnosis of primary breast cancer to BM was 38.5 month for the entire cohort (CI95% 35.4 – 43.3). The time from first diagnosis to BM was shorter for triple–negative patients (20.9 month, CI95% 15.5 – 25.9) compared with patients with HER2–positive (37.0 month, CI95% 30.5 – 42.0) or luminal tumors (48.3 month, CI95% 38.2 – 54.0) (p Conclusion: This is so far the largest analysis of breast cancer patients with BM treated in Germany. In this cohort, triple–negative subtype or more than three BM were associated with shorter survival from the diagnosis of BM. HER2 positive patients with no HER2 directed therapy after the diagnosis of BM showed a shorter survival. The recruitment of the registry is ongoing and we aim to include more than 1000 patients by the end of 2015. Citation Format: Witzel I, Loibl S, Laakmann E, Augustin D, Flock F, Dohmen H-H, Durmus G, Frank M, Hesse T, Ignatov A, Kühn T, Neunhöffer T, Park-Simon T-W, Schmidt M, Stefek A, Weide R, Würschmidt F, Fehm T, Moebus V, von Minckwitz G, Burchardi N, Mueller V. Brain metastases in breast cancer network Germany (BMBC, GBG 79): First analysis of 548 patients from the multicenter registry. [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 P6-17-08.

A subcutaneous formulation of trastuzumab to treat patients with HER2-positive breast cancer is available since August 2013. The subcutaneous formulation is administered as a fixed dose of 600 mg over a period of up to 5 minutes. The HannaH trial compared subcutaneous with intravenous administration and found comparable pharmacokinetics, efficacy and tolerability for both administration forms of trastuzumab in the neoadjuvant setting. The randomized crossover study PrefHer reported a clear preference from the patient's point of view for subcutaneous over intravenous administration of trastuzumab. The accompanying time-and-motion study reported a reduction concerning the total time spent for the institution as well as for the patient receiving trastuzumab s. c.. The experience of 7 German centers largely corresponded with the results of these studies. Patients expressed a clear preference for subcutaneous trastuzumab administration, with the time saved by the subcutaneous administration route cited as the greatest benefit. Although the existing reimbursement terms mean that centers will receive a lower remuneration, the centers' overall evaluation of the subcutaneous administration route for trastuzumab was overwhelmingly positive. The greatest benefit cited by the centers was the flexibility in scheduling patient appointments. This increased flexibility improved conditions in some centers which were experiencing pressures due to a shortage of staff, particularly at peak times. The general consensus, however, was that the remuneration systems for oncological treatments urgently need to be amended to ensure that the real costs of treatment are covered, even if the administration route has changed.Seit August 2013 steht für Patientinnen mit HER2-positivem Mammakarzinom die subkutane Applikationsform von Trastuzumab zur Verfügung, die in einer Fixdosis von 600 mg über rund 5 Minuten verabreicht wird. In der HannaH-Studie wurden in der neoadjuvanten Therapie eine vergleichbare Pharmakokinetik, Wirksamkeit und Verträglichkeit beider Applikationsformen von Trastuzumab gezeigt. Die randomisierte Crossover-Studie PrefHer wies eine deutliche Präferenz der Patientinnen für die subkutane Gabe von Trastuzumab gegenüber der intravenösen nach. In der begleitenden Time-and-Motion-Studie reduzierten sich unter der subkutanen Therapie die effektive Behandlungszeit der Patientinnen und der insgesamt für die Verabreichung von Trastuzumab notwendige Zeitaufwand des medizinischen Personals. Erfahrungen aus 7 deutschen Zentren decken sich weitgehend mit den Studienergebnissen. Vonseiten der Patientinnen bestand auch in der Praxis eine klare Präferenz für die subkutane Anwendung von Trastuzumab, wobei die Zeitersparnis durch die subkutane Anwendung als größter Vorteil wahrgenommen wurde. Trotz geringerer Vergütung aufgrund der bestehenden Abrechnungsmodalitäten fiel die Bilanz der Zentren für die subkutane Applikationsform von Trastuzumab positiv aus. Für sie bestand der wichtigste Vorteil in einer größeren Terminflexibilität, die in einigen Zentren zu einer Verbesserung einer angespannten Situation bei dünner Personaldecke und in Belastungsspitzen beitrug. Konsens war allerdings auch, dass die Vergütung onkologischer Behandlungen unbedingt angepasst werden muss, um eine Deckung des realen Betreuungsaufwands auch bei geänderten Applikationsformen zu gewährleisten.

5565 Background: Inhibition of mTOR with temsirolimus (T) might be an efficacious treatment of patients with epithelial ovarian cancer (OC) or endometrial cancer (EC). Methods: Patients (pts) with ...