Hematologic safety of palbociclib in combination with endocrine therapy in patients with benign ethnic neutropenia and advanced breast cancer.

Authors

• Filipa Lynce
• Matthew J Blackburn
• Rebecca Zhuo
• Christopher Gallagher
• Olwen M Hahn
• Maysa Abu-Khalaf
• Mahsa Mohebtash
• Tianmin Wu
• Paula R Pohlmann
• Asma Dilawari
• Shruti R Tiwari
• Ami Chitalia
• Robert Warren
• Ming Tan
• Ayesha N Shajahan-Haq
• Claudine Isaacs

Publication/Presentation Date

10-1-2021

Abstract

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, are approved to treat hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) and are associated with hematologic toxicity. African American women, who are underrepresented in CDK4/6 inhibitor clinical trials, may experience worse neutropenia because of benign ethnic neutropenia. The authors specifically investigated the hematologic safety of palbociclib in African American women with HR-positive/HER2-negative ABC.

METHODS: PALINA was a single-arm, open-label, investigator-initiated study of palbociclib (125 mg daily; 21 days on and 7 days off) plus endocrine therapy (ET) in African American women who had HR-positive/HER2-negative ABC and a baseline absolute neutrophil count ≥1000/mm

RESULTS: Thirty-five patients received ≥1 dose of palbociclib plus ET; 19 had a Duffy null polymorphism (cytosine/cytosine). There were no reports of febrile neutropenia or permanent study discontinuation because of neutropenia. Significantly more patients with the Duffy null versus the wild-type variant had grade 3 and 4 neutropenia (72.2% vs 23.1%; P = .029) and required a palbociclib dose reduction (55.6% vs 7.7%; P = .008). Patients with the Duffy null versus the wild-type variant had lower overall relative dose intensity (mean ± SD, 81.89% ± 15.87 and 95.67% ± 5.89, respectively; P = .0026) and a lower clinical benefit rate (66.7% and 84.6%, respectively).

CONCLUSIONS: These findings suggest that palbociclib is well tolerated in African American women with HR-positive/HER2-negative ABC. Duffy null status may affect the incidence of grade 3 neutropenia, dose intensity, and possibly clinical benefit.

Volume

127

Issue

19

First Page

3622

Last Page

3630

ISSN

1097-0142

Published In/Presented At

Lynce, F., Blackburn, M. J., Zhuo, R., Gallagher, C., Hahn, O. M., Abu-Khalaf, M., Mohebtash, M., Wu, T., Pohlmann, P. R., Dilawari, A., Tiwari, S. R., Chitalia, A., Warren, R., Tan, M., Shajahan-Haq, A. N., & Isaacs, C. (2021). Hematologic safety of palbociclib in combination with endocrine therapy in patients with benign ethnic neutropenia and advanced breast cancer. Cancer, 127(19), 3622–3630. https://doi.org/10.1002/cncr.33620

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

34157782

Department(s)

Administration and Leadership

Document Type

Article