Abstract OT3-05-10: A single arm phase II study of palbociclib in combination with tamoxifen as first line therapy for metastatic hormone receptor positive breast cancer

Background: Hormone receptor positive breast cancer is the most commonly diagnosed subset of breast cancer (60-65%). Endocrine therapy is effective for this subset of breast cancer, in both the adjuvant and metastatic settings. Despite advances in endocrine therapy, many patients relapse during or after completing adjuvant therapy and metastatic breast cancer remains incurable. Palbociclib is a reversible, oral, small molecule inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6). CDK4 and CDK6 together with cyclin D have important roles in regulation of the G1/S transition via regulation of the phosphorylation state of retinoblastomaprotein (Rb). Palbociclib showed significantly improved progression-free survival taken together with endocrine agents in treatment of metastatic breast cancer. Preclinical data showed that in combination with tamoxifen, palbociclib had synergistic growth inhibitory activity as well as efficacy in a model of acquired tamoxifen resistance. Combining palbociclib with tamoxifen in first line treatment of metastatic hormone receptor positive breast cancer may offers an appealing alternative to other endocrine combinations. Methods: This is a non-randomized, open-label, single-arm, multicenter, phase II study of palbociclib in combination with tamoxifen in patients with hormone receptor positive/HER2 negative advanced breast cancer. The primary objective is to determine the objective response rate (complete or partial response) based on RECIST 1.1 or MDA Criteria (for patients with bone only disease). Secondary objectives are: safety and tolerability, progression-free survival, clinical benefit rate, 2-year overall survival. Correlative objectives will explore alterations in circulating tumor DNA and changes in gene expression pattern at the time of progression. Eligibility criteria: women or men with diagnosis of hormone receptor positive/ HER2 negative locally advanced or metastatic breast cancer, not amenable to curative surgery; no prior systemic anti-cancer therapy for advanced hormone receptor positive breast cancer; adequate organ function; pre and post menopausal women are allowed. Drug administration: palbociclib dose will be 125 mg orally once daily on days 1-21 of each 28-day cycle; tamoxifen dose will be 20 mg orally once daily for every day of the 28-day cycle. As of June 2017, the study enrolled 10/71 patients and it is still open to enrollment. NCT 02668666; ocdanciu@uic.edu Citation Format: Danciu OC, Hoskins K, Tamkus D, Truica C, Blaes A, Green L, Liu L, Toppmeyer D, Wisinski K. A single arm phase II study of palbociclib in combination with tamoxifen as first line therapy for metastatic hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-05-10.