Background NEPA is the first and only fixed oral combination of a long-acting NK1receptor antagonist (RA), netupitant, and a pharmacologically distinct 5-HT3RA, palonosetron. NEPA is approved for prevention of chemotherapy (ctx)-induced nausea and vomiting (CINV) in patients (pts) receiving cisplatin-based highly emetogenic ctx (HEC) or moderately emetogenic ctx (MEC). Here we present patient-reported outcomes (PRO) of patients (pts) receiving NEPA as an antiemetic prophylaxis during platin-based chemotherapy in a prospective non-interventional study. This group of patients presents a population at high risk for CINV. Methods The ongoing prospective AkyPRO study was designed to evaluate quality of life (QoL) in 2500 pts receiving NEPA for CINV prevention in single or two-day MEC or HEC over 3 cycles. The primary endpoint QoL was recorded by FLIE questionnaires. Secondary endpoints were efficacy, reported by pts and physicians on a 4-point scale; antiemetic rescue medication, and safety. Results In this interims analysis 595 pts receiving platin-based ctx were evaluated. PRO data show that ctx-induced vomiting can be controlled very efficiently in the majority of platin-receiving pts. Between 80-90% of pts reported no impact on daily life due to vomiting and between 84-90% of pts had a complete response (no vomiting, no rescue medication) in the 3 analysed cycles, independently of which type of platin-ctx they received. Furthermore, the majority of pts (74%, 81% and 68%, respectively) reported no or mild nausea in the cisplatin-, carboplatin- and oxaliplatin-subgroup in cycle 1. However, even mild nausea seems to have a strong impact on daily life with 40% of pts receiving cisplatin- or carboplatin-based chemotherapy and 46% of oxaliplatin-receiving pts reporting an impact on daily life due to nausea in cycle 1. Conclusions NEPA was proven highly effective in controlling both vomiting and nausea over three cycles of ctx independent of the type of platin administered. Despite the reported MEC classification of oxaliplatin in contrast to the HEC classification of cis- and carboplatin, nausea was more difficult to control in oxaliplatin-receiving patients. Legal entity responsible for the study Riemser Pharma. Funding Riemser Pharma. Disclosure M. Karthaus: Advisory / Consultancy: Helsinn; Advisory / Consultancy: Riemser. J. Schilling: Advisory / Consultancy: Riemser. All other authors have declared no conflicts of interest.

Abstract Background: Further progress in the treatment of breast cancer will likely come from contributions of molecular biology and immunologic approaches. The search for druggable molecular aberrations may enable treatment based on the molecular profile. A better identification of patients with a high risk of relapse facilitates the selection of these pts for clinical trials investigating early therapeutic molecular-based interventions. Trial Design: The BRandO BiO Registry is a multi-center regional registry to record clinical, epidemiological, and biological data from patients with newly diagnosed breast and ovarian cancer at the University of Ulm, Dept. of Gynecology and 19 affiliated network hospitals and practices in the Alb-Allgäu Bodensee region (outreach area of the Comprehensive Cancer Center Ulm). Longitudinal biobanking is included with collection of paraffin-embedded samples of the primary tumor as well as blood samples at first diagnosis, after 6 and 12 months and at first relapse to isolate and investigate cell-free and germline DNA. Epidemiological, life style and quality of life (QOL) questionnaires are collected at first diagnosis, after 12, 36 and 60 months. The follow up is planned for 10 years. Eligibility criteria: Patients with primary newly diagnosed untreated breast or ovarian cancer of ≥ 18 years are eligible; primary metastatic untreated disease is allowed. Exclusion criteria comprise severe neurological or psychiatric disorders interfering with the ability to give an informed consent, no consent for registration, storage and processing of the individual disease characteristics and bio samples, and any malignant tumor in the last 3 years (except in situ disease). Specific aims: To register the majority of patients with newly diagnosed breast or ovarian cancer in all BRandO-BiO participating centers of a well-defined geographical area. To assess clinical characteristics and outcome data (event-free survival, overall survival) of these patients. To evaluate the primary tumor of all patients for mutational (druggable) aberrations. Further to assess cell-free DNA in the serial blood samples at baseline, 6 and 12 months and correlate these results with clinical outcome data as well as tumor and patient characteristics to look for early markers predicting relapse. To perform a longitudinal assessment of the patients' sociodemographic factors, comorbidities, lifestyle and QOL factors by analyzing serial questionnaires collected at recruitment and at 12, 36 and 60 months. Present accrual and target accrual: The BRandO BiO Registry started January 2016 in the Dept. of Gynecology, University of Ulm and February 2017 at the network hospitals and practices. Until June 2018, 1180 patients with primary breast or ovarian cancer have been enrolled. The current adherence to serial blood testing and serial questionnaires is good with a return rate of 90%. A sample size of 3000 patients is planned. Contact information: Jens Huober, University of Ulm, Dept of Gynecology, Breast Center, jens.huober@uniklinik-ulm.de Amelie de Gregorio, University of Ulm, Dept of Gynecology, Breast Center, Amelie.de Gregorio@uniklinik-ulm.de Citation Format: Huober J, Nagel G, Rempen A, Schlicht E, Flock F, Fritz S, Thiel F, Wiesmüller L, Felderbaum R, Heilmann V, Bekes I, Fink V, Albrecht S, De Gregorio N, Tzschaschel M, Ernst K, Wolf C, Kuhn P, Friedl T, Janni W, De Gregorio A. The BRandO BiO registry – A multicenter regional registry for patients with primary breast and ovarian cancer with longitudinal biobanking and evaluation of epidemiological, life style and quality of life factors [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 OT1-11-01.

Introduction: NEPA is a fixed dose combination of the NK1-receptor antagonist (RA) netupitant and the 5-HT3-RA palonosetron and approved for prevention of chemotherapy-induced nausea and vomiting (CINV) in pts receiving cisplatin-based highly emetogenic (HEC) or moderately emetogenic Ctx (MEC). Data from one of the pivotal studies demonstrates the safety and efficacy of NEPA in antrazyklin (A)-cyclophosphamid based Ctx, a regime recently reclassified as HEC. Both drugs are frequently used in regimens for hematology pts. A German non-interventional study investigated NEPA's efficacy and impact on quality of life in adult cancer pts by patient-related outcomes (PRO) and physicians' personal assessment under real life conditions. Primary objective was the evaluation of quality of life (QoL) in adults receiving NEPA for CINV prevention. Secondary endpoints were efficacy and safety of NEPA.

Introduction: Platinum and anthracyclin chemotherapy regimens are frequently used in hematology pts and compromised by severe acute and delayed CINV. NEPA, a fixed dose combination of the long lasting NK1-receptor antagonist (RA) netupitant and the pharmacological distinct 5HT3-RA palonosetron, has been approved by FDA and EMA for the prevention of acute and delayed CINV receiving highly emetogenic cisplatin- and AC-based as well as moderately emetogenic chemotherapy. A German non-interventional study is currently investigating NEPA's efficacy and impact on quality of life in adult cancer patients by PRO and physicians' personal assessment under real life conditions.

The combination of 5-HT3- and NK1-receptor-antagonists (RA) and dexamethasone is recommended by international guidelines for patients receiving highly emetogenic (HEC) and anthracycline / cyclophosphamide (AC) containing chemotherapy as well as for patients receiving certain moderately emetogenic chemotherapy (MEC) regimens for the prevention of chemotherapy-induced nausea and vomiting (CINV). NEPA (Akynzeo®) is a fixed combination capsule that combines the new NK1-RA netupitant and the 5-HT3-RA palonosetron. It has been approved for the prevention of acute and delayed CINV in adult cancer patients receiving cisplatin-based HEC or MEC. The objective of the study is to evaluate the quality of life of adult cancer patients undergoing MEC or HEC and receiving NEPA for CINV prophylaxis and to investigate the efficacy and safety of NEPA under real life conditions. Trial design: This non interventional study is planned to evaluate 2500 patients receiving single day or two day MEC or HEC (10-20 patients / participating center) treated in > 100 German centers (min. 125, max. 250 centers). NEPA is prescribed in accordance with the terms of the marketing authorisation. The primary endpoint is the patientś quality of life as recorded by FLIE questionnaires. Secondary endpoints include complete response (CR, no vomiting, no rescue medication), additional medication, safety data and AEs as documented by online questionnaire and patient diary. 3 consecutive chemotherapy cycles will be documented. For documentation treating physicians use the ODM QuaSi® online documentation system. All specifications in the online documentation system must be verifiable by patient records or medical test records. The trial is in ongoing. At the time of abstract submission, 178 patients treated in 129 centers (69 gynaecologic oncology, 58 medical oncology, 2 urologic oncology) had been included. The majority of patients (118) had breast cancer. Data on quality of life, efficacy and toxicity as available at the cut-off date May 2016 will be presented at the meeting. Clinical trial identification: DRKS00009316 Legal entity responsible for the study: Riemser Pharma GmbH Riemser Pharma GmbH

Fragestellung: Bei der Pathogenese des Vulvakarzinoms spielt ähnlich wie bei anderen Plattenepithelkarzinomentitäten eine Infektion mit humanem Papillomvirus (HPV) eine entscheidende Rolle. In dieser Arbeit wird der Zusammenhang zwischen HPV-Infektion, Rezidivwahrscheinlichkeit, und Tumor- sowie Patientinnencharakteristika untersucht.

Einführung: Retrospektive Daten zeigen, dass die Compliance von Patientinnen unter adjuvanter endokriner Therapie nach einer Brustkrebserkrankung bereits nach einem Jahr auf ca. 80% sinkt und im Jahr 4 wahrscheinlich nur noch bei ca. 50% liegt. PACT verfolgt das Ziel, die Therapietreue von postmenopausalen (PMP) Frauen, die adjuvant Anastrozol einnehmen, mithilfe eines standardisierten Informationsservice zu verbessern.

523 Background: Retrospective data show that compliance to adjuvant endocrine therapy for early breast cancer (EBC) may drop below 80% after 1 year and as low as 50% by year 4. PACT aims to increase treatment adherence in postmenopausal women taking adjuvant anastrozole via a standardized information service. Methods: PACT is a prospective, randomised, two-arm parallel group trial with 60 months follow-up. Women on anastrozole for hormone receptor-positive (HR+) EBC were randomized to routine clinical care alone or additional standardized information for the first 12 months of adjuvant therapy. Primary endpoint is the compliance rate after 12 months. Secondary endpoints include reasons for noncompliance, influence of baseline characteristics, and clinical outcome parameters. Compliance is evaluated via patient questionnaires, prescription data and physician recall. Results: 4,924 women were enrolled by November 2008, the average age was 64.7 years. 97.7% were ER+, 8.4% HER2+, mean tumour size 21.4 mm, 74.5% had received breast preserving surgery, 23.5% a mastectomy, 6.7% had had neoadjuvant chemotherapy and almost 40% received adjuvant chemotherapy. 85% were scheduled for adjuvant radiotherapy. Analysis of the primary endpoint compliance at 12 months will be performed after data base lock in February 2010. Conclusions: PACT is the largest prospective trial to date on compliance in HR+ EBC and aims to clarify whether standardized information services throughout year one may improve compliance to adjuvant endocrine treatment and influence outcomes in postmenopausal women with HR+ EBC. Sponsored by AstraZeneca. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Roche AstraZeneca

13546 Background: BC Patients undergoing adjuvant dose dense chemotherapy suffer high risk of febrile neutropenia (FN) due to a shortened intertreatment interval. Primary administration of Pegfilgrastim is mandatory to avoid FN when increasing dose density. In this setting our objective was to determine pharmacokinetics, safety and efficacy of Pegfilgrastim. Methods: 22 female Patients with axillary metastatic BC were administered dose-dense chemotherapy, consisting of 3×4 sequential single drug cycles of epirubicin 90 mg/m2, paclitaxel 175 mg/m2, and cyclophosphamide 600 mg/m2 was planned on a q15d schedule (similar to Citron et al. 2003). Pegfilgrastim was administered 24 hours after chemotherapy. Blood samples for pharmacokinetic studies were taken on day 8,10 and 12 of each cycle. Furthermore analysis of the absolute neutrophil count (ANC) was carried out on day 1 and 8 of each cycle. Results: The mean pegfilgrastim serum level on day 1 of each cycle was 2,88 ng/ml (SD 6,19). On day 10 1,66 ng/ml (SD 2,11) and 0,51 ng/ml (SD 3,81) on day 12 of each cycle. Highest serum levels were recorded on day 8 of cycle 1(Mean value: 12,51 ng/ml on cycle 1. SD 20,07). The minimum value was observed on day 12 of cycle 5 (Mean value 0,47 ng/ml. SD 0,38). While receiving 3 different chemotherapy agents mean decrease of pegfilgrastim serumlevel was 3,56 ng/ml in cycle 1 - 4 (SD 1,21), 0,47 ng/ml in cycle 5 - 8 (SD 4,17), and 0,49 ng/ml in cycle 9 - 12 (SD 0,06). The mean increase of ANC as measured on each cycle was 3,74 x109 (SD 0,59). These data present different extensions in each chemotherapy agent administered whereas the mean ANC growth during cycle 1 - 4 is 0,30 (SD 0,43.), 7,21 in cycle 5 - 8 (SD 1,93) and 5,31 cycle 9 - 12 (SD 0,77). The minimum of mean ANC was 2,3×109 (SD 1,48). The maximum of mean ANC was 27,8×109 (SD 10,08). 4 Patients presented with a single CTC °3 neutropenia event while no case of FN was noted at any cycle. 9 events of bone pain > CTC°1 were noted. Conclusions: Pegfilgrastim appears to remain available by maintaining stable serum levels until day 12 with absent cumulative effects. Considering the low adverse event rate we would suggest that dose dense Chemotherapy with primary Pegfilgrastim prophylaxis is a safe option for high risk breast cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen

Fragestellung: Der Verwendung prädiktiver Parameter für einen effektiven Einsatz von recombinanten Erythropoetin (rec EPO) bei der Chemotherapie assoziierten Anämie beim Mamma Ca kommt aufgrund der etwa 50% therapierefraktären Patienten eine bedeutende Rolle zu. Der lösliche Tansferrin Rezeptor (sTfR) wurde in dieser Studie als prädiktiver Frühparameter zum recEPO Einsatz bei anämischen Mammakarzinom Patientinnen unter Chemotherapie untersucht.

Zielsetzung: Patientinnen unter einer dosisdichten Chemotherapie sind einem hohen Risiko einer febrilen Neutropenie (FN) ausgesetzt. Der prophylaktische Einsatz von Pegfilgrastim ist somit unerlässlich zur Vermeidung dieser Komplikation. Wir untersuchten die chemoinduzierte Hämatotoxizität sowie die Bioverfügbarkeit von Pegfilgrastim bei Patientinnen, welche sich einer Dosisdichten Chemotherapie unterzogen.

Einleitung:Das Cervix-Carzinom ist der vierthäufigste gynäkologische Tumor der Frau in Deutschland. Entscheidend für die Therapieplanung insbesondere für die Indikationsstellung zu einer kurativen operativen Therapie ist eine möglichst exakte Ausbreitungsdiagnostik präoperativ. Neben der subjektiven bimanuellen/rektovaginalen Tastuntersuchung werden immer häufiger bildgebende Verfahren (CT/MRT) eingesetzt.

Zur Identifikation von Hochrisikogruppen unter den frühen Tumorstadien, die möglicherweise von einer adjuvanten Therapie profitieren, wären weitere Prognosefaktoren wünschenswert.

517 Background: Anthracyline-taxane combinations have the highest response rates in high risk MBC. Recently, anthracyclines and taxanes have become standards for adjuvant breast cancer chemotherapy. The addition of capecitabine to docetaxel improved overall survival in MBC. This regime was associated with a high rate of side effects (actually FN was not different from Taxotere mono - it was more the addition of cape AEs to Taxotere AEs). Earlier phase II studies with XP are able to show efficacy with better tolerability including less febrile neutropenia. Methods: Our aim was to show non-inferiority of XP to EP. The primary endpoint was progression-free survival (PFS). Secondary endpoints were toxicity and overall survival (OS).Patients (pts) were treated with 6x E 60 mg/m2 and P 175 mg/m2 d1 q21d, or with 6× X 2×1000 mg/m2 d1–14 q 21d and P 175 mg/m2 d1 q21d. Results: During a period of 2.5 y the planned 340 pts (170 in each arm) in 63 centres were recruited. The median number of cycles was 6 in both arms. The median PFS for EP was 11.8 months, and 12.3 for XP (p=ns). OS also was not different between the arms. The response rate (RECIST) was 41.0% (CR 6.6%, PR 34.4%) for EP and 41.5% (CR 8.5%, PR 33.1%) for XP. The main toxicity was myelosuppression (10% of cycles grade 3/4). Febrile neutropenia was seen in 5 cases in EP and in 1 case in XP. Skin toxicity grade 3 was observed in 5 of XP pts. Two patients stopped treatment for cardiological reasons in EP, and 4 patients for GI reasons in XP. Conclusions: This first analysis shows a comparable efficacy of the non-anthracycline regimen XP to the EP combination in first-line MBC. The toxicity is relatively low compared to other non-anthracycline containing combination therapies. XP is therefore an appropriate option for pts with anthracycline pretreated first line MBC. [Table: see text]