Abstract P1-19-20: Safety of palbociclib in African American women with hormone receptor positive HER2 negative advanced breast cancer and benign ethnic neutropenia: PALINA study
Authors: Lynce Filipa , Zhuo Rebecca , Blackburn Matthew , Gallagher Christopher , Hahn Olwen , Abu-Khalaf Maysa , Mohebtash Mahsa , Wu Tianmin , Pohlmann Paula , Dilawari Asma , Tiwari Shruti , Chitalia Ami , Warren Robert , Tan Ming , Shajahan-Haq Ayesha , Isaacs Claudine 
Published: March 2020

Abstract
Background: There are significant racial disparities in breast cancer outcomes between African American women (AAW) and Caucasian women (CW) in the US. It has been reported that AAW have more chemotherapy dose reductions than CW which results in worse clinical outcomes (Schneider BP et al. JCO Precis Oncol 2017). Given the high incidence of benign ethnic neutropenia (BEN) in AAW, we sought to evaluate the hematological safety of palbociclib in this group of patients. A polymorphism (SNP rs2814778 at chromosome 1q23.2) in the Duffy Antigen Receptor Chemokine (DARC) gene is implicated in the pathophysiology of BEN. AAW have been historically underrepresented in clinical trials including studies that led to the FDA approval of palbociclib. This diversity gap can compromise the generalizability of clinical trial results and further exacerbate minority health disparities.
Methods: PALINA is a phase II study that evaluated the hematological safety of palbociclib with endocrine therapy (ET) in 35 AAW with HR positive HER2 negative advanced breast cancer (ABC) and ANC ≥1,000 cells/mm3. Eligible patients were self-identified as African, African-American or Black, PS 0-2 and had not received a prior CDK4/6 inhibitor (CDK4/6i). Treatment included palbociclib 125mg daily for 21 days followed by 7 days off and either an aromatase inhibitor (AI) or fulvestrant per investigator discretion. Maximum time allowed on study was 12 months. Responding patients could continue palbociclib off trial. Presence of the Duffy null polymorphism as a predictive marker for neutrophil count was assessed at baseline. Metabolite and exosomal signature (proteins and RNA) of drug resistance were also evaluated at different time points and will be reported separately. Primary endpoint was the proportion of patients who completed planned oncologic therapy without the development of a hematological event defined as episodes of febrile neutropenia (FN) or treatment discontinuation due to neutropenia. A two-stage design was used to test if the completion rate of planned oncologic therapy without a hematological event was at least 80% versus if it was below 60%, with 80% power at a significance level of 5%.
Results: 35 women were enrolled from 5 different institutions. Mean age was 64 years (30-90). 9% (3/35) of patients had PS of 2. Visceral involvement was present in 51% (18/35) of patients; 60% (21/35) received an AI and 40% (14/35) received fulvestrant. Baseline median ANC was 3,100 (1,300-11,100) cells/mm3. None of the patients had FN or required discontinuation of therapy due to neutropenia. Grade 3 and 4 neutropenia were experienced by 46% (16/35) and 3% (1/35) of patients respectively. Dose delays occurred in 17 patients, and 13 patients required dose reduction (5 to 100mg and 8 to 75 mg). Clinical benefit rate (CR+PR+SD persisting for ≥6 months) was 70%. Of the 29 patients who have completed study participation, the median time on treatment was 280 days (14, 385) and 15 continued on commercial palbociclib. Last visit on study estimated for 10/2019. The Duffy polymorphism was evaluated in 94% (33/35) of patients. The Duffy null phenotype was present in 58% (19/33) of the patients. Lower baseline ANC (2,400 vs 4,300 cells/mm3, p0.006), grade 3 neutropenia (63.2 vs 21.4%, p0.003) and dose reductions (52.6 vs 7.1%, p0.009) were more common in patients with the Duffy null polymorphism.
Conclusion: This is the first trial specifically designed to evaluate the hematologic toxicity of a CDK4/6i in AAW. Although patients with the Duffy null phenotype had more dose reductions and treatment delays due to neutropenia, this did not result in episodes of FN or treatment discontinuation due to neutropenia. This analysis suggests that palbociclib with ET is safe in AAW including those with the Duffy null phenotype.
Citation Format: Filipa Lynce, Rebecca Zhuo, Matthew Blackburn, Christopher Gallagher, Olwen Hahn, Maysa Abu-Khalaf, Mahsa Mohebtash, Tianmin Wu, Paula Pohlmann, Asma Dilawari, Shruti Tiwari, Ami Chitalia, Robert Warren, Ming Tan, Ayesha Shajahan-Haq, Claudine Isaacs. Safety of palbociclib in African American women with hormone receptor positive HER2 negative advanced breast cancer and benign ethnic neutropenia: PALINA study [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 P1-19-20.