Abstract OT2-01-09: PALINA: A phase II safety study of <u>pal</u>bociclib in combination with letrozole <u>in A</u>frican American women with hormone receptor positive HER2 negative advanced breast cancer
Authors: F Lynce, A Shajahan-Haq, L Cai, D Graham, C Gallagher, M Mohebtash, L Kamugisha, N Novielli, J Castle, A Forero, C Isaacs
Journal: Cancer Research (2017)

Abstract Background:Insufficient data exist to describe the hematological safety of palbociclib in African American women (AAW) who are known to have a high incidence of benign ethnic neutropenia (BEN). The studies that led to the FDA approval of palbociclib (PALOMA 1 and 3) only included participants with baseline absolute neutrophil count (ANC) of ≥1500/mm3. The standard lower limit of ANC of 1500/mm3 for initiation of treatment in those with BEN has been previously challenged. In this current study, we propose to lower the ANC cutoff for enrollment to 1000/mm3. Trial design: PALINA is a phase II study evaluating the hematological safety of palbociclib with letrozole in 35 AAW with hormone receptor (HR) positive HER2 negative advanced breast cancer and ANC ≥1000/mm3. Patients enrolled will receive palbociclib 125mg daily for 21 days followed by 7 days off and letrozole 2.5mg daily. For patients enrolled with baseline ANC between 1000-1499/mm3, initial dose of palbociclib will be 100mg daily for 21 days followed by 7 days off. Presence of Duffy Null Polymorphism (SNP rs2814778) as a predictive marker for neutrophil count will be assessed at baseline. Metabolite and exosomal signature (proteins and RNA) of drug resistance will be evaluated at different time points. Main eligibility criteria: Self-identified Black, African or AAW of ≥ 18 years of age with proven diagnosis of advanced HR-positive, HER2-negative breast cancer; ECOG performance status 0-2; ANC ≥ 1,000/mm3 and no prior receipt of CDK4/6 inhibitors. Specific aims: The primary endpoint is the proportion of patients who complete planned oncologic therapy without the development of a hematological event defined as episodes of febrile neutropenia and treatment discontinuation due to neutropenia. Additional endpoints include: number of patients who required dose delays or dose reductions in palbociclib attributed to neutropenia; rate of grade 3/4 neutropenia; clinical benefit rate at 24 weeks; correlations between metabolite and exosomal signature with disease response; correlations between baseline ANC prior to cancer diagnosis and the Duffy Null polymorphism with hematological safety. Statistical methods: The study is designed to assess the rate of completion of planned therapy in the absence of a hematological event defined as episodes of febrile neutropenia and treatment discontinuation due to neutropenia. Simon's two-stage design with a maximum of 35 patients is used. The null hypothesis that the true completion rate is 60% will be tested against a one-sided alternative. This design yields a type I error rate of 0.05 and power of 80% when the true completion rate is 80%. Present accrual and target accrual: The Institutional Review Board at Georgetown University Medical Center (GUMC) has approved the study. Enrollment of the first patient is expected in July 2016 with a total of 35 patients planned to be recruited. The recruitment sites are MedStar Georgetown University Hospital and other hospitals of the Georgetown MedStar Cancer Network, Hackensack University Medical Center and University of Alabama at Birmingham. This trial is funded by an ASPIRE Breast Cancer Research Award from Pfizer. Citation Format: Lynce F, Shajahan-Haq A, Cai L, Graham D, Gallagher C, Mohebtash M, Kamugisha L, Novielli N, Castle J, Forero A, Isaacs C. PALINA: A phase II safety study of palbociclib in combination with letrozole in African American women with hormone receptor positive HER2 negative advanced breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-09.