Abstract P2-17-03: Real-world benefit of CDK4/6 inhibitor and endocrine therapy combination in metastatic breast cancer and correlation with neutropenia
Authors: Jenneman Dakota , Zhong Xiaojun , Ma Junjie , Sun Weihong , Han Heather , Soliman Hatem , Loftus Loretta , Costa Ricardo , Armaghani Avan , Soyano Aixa , Czerniecki Brian , Lee M. Catherine , Kiluk John , Khakpour Nazanin , Hoover Susan , Laronga Christine , Khong Hung T 
Published: March 2020

Abstract
Background: Combination of a CDK4/6 inhibitor plus endocrine therapy has been shown to significantly improve the progression free survival (PFS) in patients with hormone-receptor (HR)+, HER2- metastatic breast cancer. The aims of this retrospective study was: 1) to evaluate the real-world benefit of palbociclib plus endocrine therapy as the first line treatment in HR+, HER2- metastatic breast cancer (mBC) and 2) to correlate efficacy of the combination with neutropenia (which is a common toxicity of CDK4/6 inhibitors). Methods: This study included HR+, HER2- advanced mBC patients who were treated with palbociclib plus an endocrine therapy (mainly letrozole) at Moffitt Cancer Center between January 1, 2015 and March 1, 2018. The PFS was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were investigated using the univariable and multivariable Cox models. Results: A total of 165 patients were included in this retrospective cohort study. The median PFS of the full cohort was 24.19 months (95% CI 18.93 to not reached). For patients with bone metastasis only (n = 54), the median PFS was not reached (95% CI 18.21 to not reached). For patients with non-bone-only metastasis (n = 111), the median PFS was 24.19 months (95% CI 16.33 to 33.82). Patients with higher absolute neutrophil counts (ANC) are at high risk of disease progression (HR 1.15; 95% CI 1.03 to 1.29, p = 0.013). We did not find a significant association between the value of NLR and the risk of disease progression (HR 1.07 95% 0.97 to 1.18, p = 0.203). Both ANC and NLR were used as a time dependent variable. Conclusion:The effectiveness of palbociclib plus letrozole in the treatment of HR+, HER2- metastatic breast cancer in the real-world setting was found to be similar to the results from the PALOMA-2 trial. In addition, patients with a higher ANC were found to have a higher risk for early disease progression. This has implication for clinical practice [i.e., frequent dose delay and/or dose reduction based on ANC threshold of 1000/uL may not be an optimal approach. Since infection is rare, it is reasonable to reduce this threshold to a lower level such as 750-800/uL].
Citation Format: Dakota Jenneman, Xiaojun Zhong, Junjie Ma, Weihong Sun, Heather Han, Hatem Soliman, Loretta Loftus, Ricardo Costa, Avan Armaghani, Aixa Soyano, Brian Czerniecki, M. Catherine Lee, John Kiluk, Nazanin Khakpour, Susan Hoover, Christine Laronga, Hung T Khong. Real-world benefit of CDK4/6 inhibitor and endocrine therapy combination in metastatic breast cancer and correlation with neutropenia [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-03.