Abstract OT2-01-09: ABEMACARE: Abemaciclib in Combination with Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients with Symptomatic Visceral Metastases or High Tumor Burden – A prospective multicenter observational study

ABEMACARE: Abemaciclib in Combination with Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients with Symptomatic Visceral Metastases or High Tumor Burden – A prospective Multicenter Observational Study Sophia Ramsperger, Franziska Kotzur, Lothar Müller, Stephan Seitz, Peter A. Fasching, Stefanie Jilg, Dorothea Fischer, Silvia Egert-Schwender, Victoria Kehl, Ute Reuning, Lukas Rief, Romina Rösch, Holger Bronger, Christof Winter, Marion Kiechle, Johannes Ettl Background: Combined endocrine therapy with Cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors and aromatase inhibitor (AI) or Fulvestrant has become standard of care in first line therapy of estrogen receptor (ER) positive, HER2 negative metastatic breast cancer. Numeral trials have shown excellent results regarding disease control and survival while maintaining quality of life for patients. In the MONARCH 2 and MONARCH 3 trials, patients with liver metastases derived a particularly large benefit from the use of Abemaciclib. Nevertheless, in real world many patients with endocrine sensitive metastatic breast cancer are still being treated with chemotherapy in first line. Symptomatic visceral disease and/or high tumor burden are often seen as reasons for upfront chemotherapy even in the absence of visceral crisis. In this specific patient population Abemacare aims at determining the efficacy of Abemaciclib in combination with endocrine therapy as first line treatment. Further, the question is addressed, whether circulating tumor DNA might serve as a predictive biomarker for early tumor response. Study Design: Abemacare is a prospective multicenter noninterventional, observational study. 96 patients in 10 German cancer centers who receive first line Abemaciclib in combination with AI or Fulvestrant are planned to be enrolled. Recruitment started in December 2020. As of July 1st 2022, 51 patients have been included in six study sites. Patients with documented ER-positive, HER2-negative metastatic breast cancer and 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 (> 2x ULN)) or signs of high tumor burden (e.g. LDH > 399 U/l with K+ in normal range, abnormal CEA or CA 15-3 level (> 2x ULN), radiographic signs of lymphangiosis of the lung, cytologically proven bone marrow infiltration). Patients with prior therapy with a CDK 4/6 inhibitor in any setting or first line therapy for metastatic disease are excluded from the trial. Primary endpoint is best objective response rate (ORR) defined by the proportion of patients who are evaluated using RECIST V1.1 as having partial (PR) or complete response (CR) while being on study treatment. 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. Plasma samples for ctDNA are being collected at d1 and d15 of cycle 1 and d1 of cycle 2 and 3. 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. NCT04681768 a>Disclosure(s): Johannes Ettl, n/a: Amgen, Celgene, Eisai, Myriad, Teva.: Consulting Fees (e.g., advisory boards) (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing); Pfizer, Pierre Fabre, Lilly, Roche, AstraZeneca, Daiichi, Gilead, Seagen: Consulting Fees (e.g., advisory boards) (Ongoing) Ramsperger Sophia, n/a: No financial relationships to disclose Franziska Kotzur, n/a: No financial relationships to disclose Lothar Müller, n/a: No financial relationships to disclose Stephan Seitz, n/a: AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); GE; Gedeon-Richter; GSK; Lilly;: Consulting Fees (e.g., advisory boards) (Ongoing) Peter A. Fasching, MD: Agendia: Consulting Fees (e.g., advisory boards) (Ongoing); AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing); Biontech: Contracted Research (Ongoing); Cepheid: Contracted Research (Ongoing); Daiichi Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing); Eisai: Consulting Fees (e.g., advisory boards) (Ongoing); Genentech: Consulting Fees (e.g., advisory boards) (Ongoing); Gilead: Consulting Fees (e.g., advisory boards) (Ongoing); Lilly: Consulting Fees (e.g., advisory boards) (Ongoing); Merck Sharp & Dohme: Consulting Fees (e.g., advisory boards) (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing); Pierre Fabre: Consulting Fees (e.g., advisory boards) (Ongoing); Roche: Consulting Fees (e.g., advisory boards) (Ongoing); Sanofi Aventis: Consulting Fees (e.g., advisory boards) (Ongoing); SeaGen: Consulting Fees (e.g., advisory boards) (Ongoing) Stefanie Jilg, n/a: No financial relationships to disclose Dorothea Fischer, n/a: No financial relationships to disclose Silvia Egert-Schwender, n/a: No financial relationships to disclose Kehl Victora, n/a: No financial relationships to disclose Ute Reuning, n/a: No financial relationships to disclose Romina Rösch, n/a: No financial relationships to disclose Lukas Rief, n/a: No financial relationships to disclose Holger Bronger, n/a: No financial relationships to disclose Christof Winter, n/a: No financial relationships to disclose Marion Kiechle, n/a: Myriad Genetics, Bavarian KVB, DKMS Life, BLAEK, TEVA, Exeltis. Equity owner: Therawis Diagnostic GmbH, AIM GmbH.: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing) Citation Format: Johannes Ettl, Ramsperger Sophia, Franziska Kotzur, Lothar Müller, Stephan Seitz, Peter A. Fasching, Stefanie Jilg, Dorothea Fischer, Silvia Egert-Schwender, Kehl Victora, Ute Reuning, Romina Rösch, Lukas Rief, Holger Bronger, Christof Winter, Marion Kiechle. ABEMACARE: Abemaciclib in Combination with Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients with Symptomatic Visceral Metastases or High Tumor Burden – A prospective multicenter observational study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-09.