ABCE4 study: estetrol for treatment of advanced ER+ breast cancer

15th St.Gallen International Breast Cancer Conference / The Breast 32S1 (2017) S22–S77

Table 1. PK parameters Parameter (Unit)

AUCinf (h* μg/mL) AUClast (h* μg/mL) Cmax (μg/mL) 1 Tmax (h) T1/2 (h)

Geometric Mean (CV) CT-P6 (n = 35)

Trastuzumab (n = 35)

20012.77(18.70) 18649.39 (19.26) 131.03 (17.92) 1.550 (1.52, 6.00) 186.13 (19.04)

20203.75 (17.56) 18781.49 (18.83) 135.66(15.49) 1.517(1.52, 6.02) 180.45 (20.44)

1

Median (min, max) for Tmax

Conclusions: CT-P6 and trastuzumab were bioequivalent, as measured by primary PK endpoints (AUCinf, AUClast, and Cmax) in healthy male volunteers. The safety and immunogenicity profile of CT-P6 were similar to that of trastuzumab. Disclosure of Interest: No significant relationships. P138 Does changing classification for multifocal and multicentric breast cancers alter breast conservation rates? M. Tan1, N. Sitoh2 *, Y.R. Sitoh1. 1MammoCare The Breast Clinic & Surgery, Singapore, Singapore, 2Yong Loo LIn School of Medicine, National University of Singapore, Singapore, Singapore Aims: Breast conservation therapy (BCT) is considered to be an acceptable treatment option for multifocal (MF) multicentric (MC) breast cancer (BC) if negative margins are achieved for all tumour foci and radiotherapy is administered. However, MFMCBC lacks a classification which offers a roadmap to enable a consistent surgical approach for BCT. MFMCBC is conventionally defined by quadrants, with tumours occurring in the same quadrant defined as MF and foci in different quadrants MC disease. This quadrant classification does not provide an intuitive surgical approach. To achieve the latter for BCT in MFMCBC, a segment classification was proposed. There was some concern that the use of a segment classification would artificially augment BCT rates for MC tumours. This study was therefore performed to explore if the use of different definitions would significantly affect successful BCT rates for MFMCBC. Patients and Methods: Consecutive patients who were diagnosed to have MFMCBC and treated at a single institution between Jan 2009 & Dec 2011 were included in the study. Diagnosis was made on the basis of preoperative biopsy and postoperative histologic evaluation. Successful BCT for MFMCBC were defined as attainment of negative margins for all foci, followed by completion of adjuvant therapy. Results: A total of 40 patients were diagnosed with MFMCBC during the study period. Based on the segment classification, 24 (60%) were MF & 16 (40%) were MC lesions. BCT rates were 87.5% & 81.3% for MF & MC disease, respectively. If the tumours were categorised based on quadrants, then 28 (70%) would be MF and 12 (30%) would have MC disease, with BCT rates of 85.7% & 83.3% respectively. Five-year overall survival and disease-free survival for the entire cohort were 95% & 92.5%, respectively. A separate analysis demonstrated that all patients were at least satisfied with their aesthetic result and none rated their cosmetic outcome as fair or poor. Conclusion: The majority of women with MFMCBC underwent successful BCT in this study. The classification of MFMCBC according to segments or quadrants did not affect BCT rates. However, the segment classification provides an additional dimension by offering a roadmap for a consistent reductionist surgical approach to achieve BCT with reasonable cosmesis and acceptable overall survival. Disclosure of Interest: No significant relationships.

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P139 Rationale and design of the real-world Hellenic disease management patterns with everolImus for women with hormone-receptor-positive, human epidermal growth factor ReceptOR-2 negative advanced breast cancer (The MIRROR) study C. Karanikiotis1, G. Kesisis2 *, I. Xanthakis2, A. Alexopoulos3, V. Barbounis4, C. Panopoulos5, C. Andreadis6, C. Papadimitriou7. 1 Department of Medical Oncology, 424 Army General Hospital, Thessaloniki, Greece, 2Medical Oncology, “Saint Luke” Private Hospital, Thessaloniki, Panorama, Greece, 3Hygeia Hospital, Athens, Greece, 4 Oncology Clinic, Metropolitan Hospital, Athens, Greece, 5Medical Oncology Unit, Athens Euroclinic, Athens, Greece, 6Third Department of Clinical Oncology, Theagenio Cancer Hospital, Thessaloniki, Greece, 7 Dept. of Oncology, National and Kapodistrian University of Athens, School of Medicine, IASO Hospital, Athens, Greece Aims: Treatment paradigms and factors guiding physicians’ treatment decision-making in hormone receptor (HR)-positive advanced breast cancer (aBC) in the routine clinical care in Greece have not been methodically captured and documented. In this perspective, the MIRROR study aims to provide real-world evidence on utilization patterns of the first-in-class mTOR inhibitor (everolimus) in the early lines of aBC treatment in Greece and specifically to examine the rate of its inclusion in the first versus second line treatment strategy, as well as to record prior treatment sequencing patterns employed and to identify potential patient and disease characteristics that affect everolimus inclusion in the first line setting. Methods: This is a multicenter, single-visit, observational drug utilization study in Greece, which plans to enrol 100 female adult outpatients with HR positive, human epidermal growth factor-2 negative aBC who have been prescribed everolimus in the first or second line setting and have not received therapy more than six months prior to enrolment. Data collection is performed through medical chart review as per the routine practice by means of an electronic data capture system. Up to 12 study sites diversely distributed throughout Greece consisting of hospital-based breast cancer specialists are planned to consecutively enrol the first eligible and consented patients attending their clinic. Site selection has been based on a documented and constructed feasibility assessment process accounting for the site’s recruitment potential. Results: This study is currently underway. The first patient was enrolled on 20 July 2016 and enrolment is projected to be completed by the end of June 2017. The final clinical study report is expected to be ready by early 2018. Conclusions: The MIRROR study will provide essential insights on the utilization of everolimus in aBC routine clinical care settings and on the potential factors associated with physicians’ treatment decision in the first line setting of metastatic BC patients in Greece. Disclosure of Interest: All authors are investigators that participate in this Novartis-sponsored study P140 ABCE4 study: estetrol for treatment of advanced ER+ breast cancer C. Verhoeven1*, M. Schmidt2, A. Dutman1, H.C. Bennink1. Pantarhei Oncology BV, Zeist, Netherlands, 2Klinik und Poliklinik für Geburtshilfe und Frauengesundheit, University of Mainz, Mainz, Germany 1

Introduction: High dose of estrogens (HDEs) was the endocrine treatment of choice in postmenopausal women with advanced breast cancer for several decades. In the 1970s, estrogen therapy was replaced by tamoxifen. Although not more effective than high dose of estrogens, tamoxifen was shown to be less toxic and therefore considered to be the preferred agent. Recently, estrogen therapy for breast cancer has gained new interest as several clinical studies showed anti-tumour efficacy with HDEs in heavily pre-treated patients with advanced breast cancer in an estrogen deprived

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Poster Abstracts I / The Breast 32S1 (2017) S22–S77

setting. HDEs are an effective treatment for breast cancer but they have a negative safety reputation, especially of having side effects related to the cardiovascular (CV) system. The fetal estrogen estetrol might be a new treatment option as estetrol has less interference with liver function and is expected be less harmful for the CV system compared to other estrogens. Hypothesis/aim: The fetal estrogen estetrol may have anti-tumour effects in patients with advanced ER+ breast cancer. It will most likely also improve patient’s quality of life by reducing symptoms of estrogen deficiency. Study design and methods: This is a multi-center, open-label, phase I/IIa trial, dose-escalation study with a 3 + 3 cohort design to determine the recommended dose of estetrol for the treatment of patients with advanced breast cancer. Cohorts of at least 3 patients will receive escalating doses of 20, 40 and 60 mg estetrol until the nontolerable dose is determined or the maximum anticipated dose of 60 mg is reached. Patients will be treated once daily by oral administration of estetrol for 12 weeks. In total 9–18 patients with advanced ER+ breast cancer will be enrolled at three centers in Germany. Results: Non-clinical and clinical studies performed so far give a strong indication that estetrol treatment might have a favourable effect on breast cancer. DMBA in vivo studies have shown that estetrol is able to prevent tumour development and existing tumours decrease in size/disappear, both dose dependently. In a human pilot study, performed in 30 women with recently diagnosed breast cancer, estetrol treatment had a significant pro-apoptotic effect on tumour tissues. Conclusion: Data from the ABCE4 study in patients with advanced breast cancer are expected to confirm our hypothesis. Disclosure of Interest: Employee and shareholder of pantarhei oncology P141 First-line ribociclib + letrozole in patients with HR+, HER2– advanced breast cancer (ABC) who received prior (neo)adjuvant therapy: a subgroup analysis of the MONALEESA-2 trial P. Conte1 *, S. Paluch-Shimon2, H.A. Burris3, K. Petrakova4, K.L. Blackwell5, C. Dittrich6, C.L. Arteaga7, S. Sutradhar8, M. Miller8, M. Campone9. 1University of Padova and Istituto Oncologico Veneto, IRCCS, Padova, Italy, 2Sheba Medical Center, Ramat Gan, Israel, 3Sarah Cannon Research Institute, Nashville, USA, 4Masaryk Memorial Cancer Institute, Brno, Czech Republic, 5Duke University Medical Center, Durham, USA, 6Center for Oncology and Hematology, Kaiser-Franz-JosefSpital, Vienna, Austria, 7Vanderbilt-Ingram Cancer Center, Nashville, USA, 8Novartis Pharmaceuticals Corporation, East Hanover, USA, 9 Institut de Cancérologie de l’Ouest/René Gauducheau, Saint-Herblain, France Aims: Endocrine therapy (ET) is a standard adjuvant therapy for hormone receptor-positive (HR+), HER2-negative (HER2–) breast cancer; in some cases, (neo)adjuvant ET or chemotherapy (CT) is administered. Whether such treatments alter disease biology or response to subsequent therapy is unclear. Here we report on patients ( pts) who received (neo)adjuvant ET or CT prior to MONALEESA-2 (NCT01958021), a randomized Phase 3 study of first-line ribociclib (a selective cyclin-dependent kinase [CDK]4/6 inhibitor) + letrozole vs placebo + letrozole for HR+, HER2– ABC. Methods: Pts were randomized 1:1 to receive ribociclib (600 mg/day; 3-weeks-on/1-week-off ) + letrozole (2.5 mg/day; continuous) or placebo + letrozole. Prior CDK4/6 inhibitors were prohibited. Prior neo(adjuvant) therapy was permitted; a >12-month disease-free interval (DFI) was required if letrozole/anastrozole were included; no DFI was required for other (neo)adjuvant ET. Primary endpoint: locally assessed progression-free survival (PFS), with subgroup analyses in pts who had prior (neo)adjuvant therapy. Results: Of 668 pts (334 per arm), 220 (65.9%; ribociclib + letrozole) and 221 (66.2%; placebo + letrozole) pts had recurrent breast cancer. In the ribociclib + letrozole vs placebo + letrozole arms, 146 (43.7%) vs

145 (43.4%) pts had prior (neo)adjuvant CT and 175 (52.4%) vs 171 (51.2%) pts had prior (neo)adjuvant ET; 123 (36.8%) vs 120 (35.9%) pts had prior (neo)adjuvant CT and ET. In the full population, PFS was significantly prolonged in the ribociclib + letrozole arm (hazard ratio [HR] = 0.556; 95% CI 0.429–0.720; P = 3.29 × 10–6). This risk reduction was consistent in pts who had prior (neo)adjuvant CT (HR = 0.548; 95% CI 0.384–0.780) or ET (HR = 0.538; 95% CI 0.384–0.754), and those who had no prior (neo)adjuvant CT (HR = 0.548; 95% CI 0.373– 0.806) or ET (HR = 0.570; 95% CI 0.380–0.854). Safety data were broadly consistent across subgroups and the full population. In the ribociclib + letrozole arm, the most common all-grade adverse events (AEs; ≥45% of pts) in each subgroup were neutropenia and nausea; neutropenia was the most common Grade 3/4 AE. Conclusions: The combination of ribociclib + letrozole was well tolerated and prolonged PFS vs placebo + letrozole in pts with HR+, HER2– ABC, regardless of prior (neo)adjuvant CT or ET. Disclosure of Interest: Dr. Blackwell reports grants from Novartis, personal fees from Novartis, during the conduct of the study; personal fees from Amgen, personal fees from AstraZeneca, grants from Celgene, personal fees from Celgene, grants from Genentech, personal fees from Genentech, personal fees from Eli Lilly, personal fees from Eisai, personal fees from GE Healthcare, personal fees from Hospira, grants from Pfizer, personal fees from Pfizer, personal fees from Puma, personal fees from Roche, personal fees from Rockwell, personal fees from Spectrum, personal fees from Inctyte, personal fees from Sandoz, personal fees from Janssen, personal fees from Bayer, outside the submitted work; Dr. Dittrich reports grants from Novartis, during the conduct of the study; personal fees from Novartis, outside the submitted work; Dr. Campone reports grants and personal fees from NOVARTIS, during the conduct of the study; grants from ROCHE, grants and personal fees from ASTRA ZENECA, grants and personal fees from Tessaro, grants and personal fees from Pfizer, outside the submitted work; M Miller is a Novartis employee and owns Novartis stock; S Sutradhar is an employee of Novartis

Radiotherapy/IORT P145 DIBH radiotherapy in left-sided breast cancer patients using an optical surface scanning system S. Corradini1 *, S. Schönecker1, M. Pazos1, P. Freislederer1, D. Reitz1, N. Ditsch2, V. von Bodungen2, R. Würstlein2, N. Harbeck2, C. Belka1. 1 Department of Radiation Oncology, LMU Munich, Germany, 2Breast Center, Dept. OB &GYN, LMU Munich, Germany Background: There is a potential for adverse cardiovascular effects in long-term breast cancer survivors following adjuvant radiotherapy (RT). For this purpose, the deep inspiration breath-hold technique (DIBH) has been introduced into clinical practice, in order to maximally reduce the radiation dose to the heart, as the heart moves out of the radiation field with DIBH. Patients and methods: A total of 38 patients with left-sided breast cancer following breast conserving surgery were analysed. Patients were treated with normofractionated and hypofractionated radiotherapy protocols. Patient surface data and respiratory parameters were acquired using the laser surface scanner Sentinel (C-RAD AB, Uppsala, Sweden) during CT acquisition in free breathing (FB) and DIBH. Dual treatment plans were created and dosimetric output parameters of organs at risk were compared. For treatment application, the optical surface scanner Catalyst (C-RAD AB, Uppsala, Sweden) was used and gating control was performed with an individual audio and video glasses-based feedback system. Results: 30 of 38 patients were treated using normofractionated treatment protocols. In these patients, reduction of the mean heart dose for DIBH compared to FB was 43.2% (2.45 to 1.39 Gy; p < 0.001). The maximum doses to the heart and LAD were reduced by 47.2%