Abstract
Background: Palbociclib, a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor, in combination with letrozole or fulvestrant has been demonstrated to prolong the progression-free survival (PFS) in patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer. In efforts to mitigate neutropenic toxicities, oncologists in real-world practice have prescribed alternative dosing strategies with palbociclib, yet the implication on PFS is unknown. Methods: We conducted a retrospective, observational chart review of all female patients at our clinics with HR+, HER2- metastatic breast cancer receiving palbociclib in combination with either letrozole or fulvestrant with a first dose initiated between June 2016 and December 2018 and followed their disease course until 30 April 2020. Results: The median PFS for all clinic patients receiving palbociclib and letrozole (n = 63) was 40.8 months (95% confidence interval (CI) 25.6–not estimable) and 16.97 months (95% CI 8.57–not estimable) for patients receiving palbociclib and fulvestrant (n = 11). We identified seven alternative dosing strategies prescribed by oncologists, the most prevalent being prescribing palbociclib for three weeks on and two weeks off (n = 8). The Kaplan–Meier curves for PFS in patients receiving letrozole and palbociclib prescribed alternative dosing strategies appear to diverge from monograph dosing early in the treatment. Many patients prescribed palbociclib using alternative dosing strategies continued to be observed even by the 18-month timepoint. The prevalence of grade 4 neutropenia was lower for patients on palbociclib with letrozole, suggesting a possible mitigation of severe neutropenia with alternative dosing strategies. Conclusions: We conclude that alternative dosing strategies used by oncologists such as prescribing palbociclib for three weeks on, two weeks off may achieve comparable disease control while mitigating neutropenic toxicities when compared to standard monograph dosing recommendations, prolonging treatment tolerability and adherence. Further large-scale studies are needed to confirm these results for future clinical adoption.
Highlights
IntroductionBreast cancer is the second most diagnosed cancer worldwide and the most commonly diagnosed cancer in women [1,2]
In the landmark PALOMA-2 study, the combination of palbociclib and letrozole in advanced breast cancer resulted in a median progression-free survival (PFS) of 24.8 months compared with 14.5 months in the placebo-letrozole group (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.46 to 0.72, p < 0.001) [10]
The aim of our study was to identify unique alternative dosing strategies of palbociclib prescribed by oncologists in a real-world setting and assess their impact on PFS in patients with hormone receptor (HR)-positive, human epidermal growth factor 2-negative (HER2-)negative metastatic breast cancer
Summary
Breast cancer is the second most diagnosed cancer worldwide and the most commonly diagnosed cancer in women [1,2]. While early breast cancer has excellent prognosis, metastatic breast cancer remains incurable with current therapies [3] Since their discovery, hormone receptor (HR) and human epidermal growth factor 2 (HER2) have been essential biomarkers that predict disease prognosis and guide treatment decisions [4,5]. Endocrine therapy was the first-line treatment for metastatic HR-positive, HER2-negative breast cancers, but the development of resistance towards endocrine therapy would subsequently necessitate chemotherapy [7]. This has led research efforts towards alternative pharmacotherapy targeting cell cycle pathways. Palbociclib, a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor, in combination with letrozole or fulvestrant has been demonstrated to prolong the progression-free survival (PFS) in patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer. Further large-scale studies are needed to confirm these results for future clinical adoption
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