Abstract OT-26-01: ABEMACARE: Abemaciclib in combination with endocrine therapy as first line therapy in metastatic breast cancer patients with symptomatic visceral metastases or high tumor burden
Authors: Kotzur Franziska , Bidner Helen , Bronger Holger , Egert Silvia , Fasching Peter A , Fischer Dorothea , Kehl Victoria , Lück Hans-Joachim , Müller Lothar , Reuning Ute , Rief Lukas , Rösch Romina , Seitz Stephan , Winter Christof , Kiechle Marion , Ettl Johannes 
Published: February 2021

Abstract
Background:
Cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors in combination with endocrine therapy are well established in the therapy of estrogen receptor (ER) positive, HER2 negative metastatic breast cancer. They have shown excellent results regarding disease control and survival in numerous trials while maintaining good quality of life for patients. In the subgroup analysis of the MONARCH 2 and MONARCH 3 trials, patients with liver metastases derived a particularly large benefit from the combined endocrine treatment with Abemaciclib. Despite this evidence, in real world many patients with endocrine sensitive metastatic breast cancer are still being treated with first line chemotherapy. Especially in patients with symptomatic visceral disease and/or high tumor burden, use of upfront chemotherapy remains common even in the absence of visceral crisis. With this study we aim to determine the efficacy of Abemaciclib in combination with endocrine therapy as first line treatment in this specific patient population.
Study design:
In this prospective multicenter observational study, we intend to enroll 120 patients in 10 German cancer treatment centers who will receive first line therapy with Abemaciclib in combination with endocrine therapy within clinical routine. Recruitment is planned to start in August 2020. Patients with documented ER positive, HER2 negative metastatic breast cancer with measurable visceral disease are eligible if they fulfill one of the following inclusion criteria: Presence of clinical signs or symptoms of visceral disease (e.g. pleural effusion, ascites, abdominal pain from liver or peritoneal metastases, dyspnea from pleural effusion or lymphangiosis of the lung, elevated liver enzymes or bilirubin level (&gt; 2x ULN)) or signs of high tumor burden (e.g. LDH &gt; 399 U/l with K in normal range, abnormal CEA or CA 15-3 level (&gt; 2x ULN), radiographic signs of lymphangiosis of the lung, cytologically proven bone marrow infiltration). Patients may have received chemotherapy or endocrine therapy in the adjuvant setting, but no prior therapy with CDK 4/6 inhibitors and no first line therapy for metastatic disease. Primary endpoint is best objective response rate (ORR) defined by the proportion of patients who are evaluated as having partial (PR) or complete response (CR) while being on study treatment using RECIST V1.1. ORR will be analyzed using the one group χ2 test at the 5% significance level. The test hypotheses are as follows: H0: ORR = 0.43, HA: ORR ≠ 0.43. In addition, ORR will be reported with a 95% CI.Several additional endpoints regarding disease control and patient reported outcomes will also be evaluated. At the same time translational research to identify possible early predictive biomarkers for tumor response (e.g. circulating tumor DNA) will be conducted.
Contact information:
For further information please contact the leading physician Dr. Johannes Ettl via johannes.ettl@tum.de
This study is supported by Eli Lilly and Company.
Citation Format: Franziska Kotzur, Helen Bidner, Holger Bronger, Silvia Egert, Peter A Fasching, Dorothea Fischer, Victoria Kehl, Hans-Joachim Lück, Lothar Müller, Ute Reuning, Lukas Rief, Romina Rösch, Stephan Seitz, Christof Winter, Marion Kiechle, Johannes Ettl. ABEMACARE: Abemaciclib in combination with endocrine therapy as first line therapy in metastatic breast cancer patients with symptomatic visceral metastases or high tumor burden [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-26-01.