Alternative palbociclib dosing schedules for hormone receptor-positive and HER2-negative metastatic breast cancer.

Abstract

Introduction: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib is associated with a high incidence of neutropenia. Treatment continuation using the standard dosing schedule (3 consecutive weeks of oral administration followed by 1-week off-treatment: 3/1 schedule) can be difficult and other dosing schedules have been previously adopted. We aimed to investigate whether alternative dosing schedules can be used effectively to continue palbociclib.

Methods: This study included all patients who received palbociclib for hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2-MBC) at Ogaki Municipal Hospital between January 2018 and November 2023. Reasons for treatment discontinuation, changes in treatment administration, treatment duration, relative dose intensity (RDI), overall response rate (ORR), clinical benefit rate (CBR), and adverse events were retrospectively investigated using electronic medical records.

Results: On November 30, 2023 (a data censor date), patients who discontinued or continued palbociclib on the 3/1 schedule were classified into the 3/1 schedule group (n=20), and those who started a 3/1 schedule (partly on a 2/2 schedule) and then switched to the 3/2 schedule or the 2/2 schedule (2 consecutive weeks of oral administration followed by 2 weeks off) were classified into the 3/2 (n=10) or 2/2 schedule groups (n=18), respectively. For the 3/1, 3/2, and 2/2 schedule groups, respectively, the median treatment duration was 255.5, 1253.0, and 923.0 days (p=0.0013), the median RDI (%) was 71.0%, 69.2%, and 40.8% (p<0.001), and the ORR was 15.0%, 80.0%, and 50.0% (p=0.002), while the CBR was 55.0%, 100%, and 72.2% (p=0.028).

Conclusion: Dosing schedules other than the standard 3/1 schedule can be used to continue palbociclib with HR+/HER2-MBC while ensuring therapeutic efficacy. Alternative dosing schedules look promising and need further research (preferably, prospective studies) with a larger sample size and longer follow-up to validate treatment efficacy.