Abstract
PurposeSince the widespread implementation of adding palbociclib to endocrine therapy in clinical practice, myelosuppression is becoming increasingly recognized as a toxicity that may lead to dose modification. We aimed to characterize toxicities observed with palbociclib resulting in dose modifications and prescriber preferences in modifying palbociclib dosage in response to treatment-related toxicities outside the context of a clinical trial.MethodsWe conducted a single institution, retrospective study of treatment-related adverse events (AEs) resulting in modifications in dose and schedule and the methods by which dose modifications occurred in patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer receiving palbociclib and endocrine therapy.ResultsFrom 2/2015 to 10/2016, 100 patients were identified for inclusion in this study. Treatment with palbociclib and endocrine therapy resulted in dose modifications in 38.0% of patients due to AEs with 18.4% requiring subsequent dose changes. Most palbociclib dose modifications occurred during the first 2 cycles. Grade 3–4 neutropenia accounted for 54.8% events of palbociclib dose modification. Most providers (65.8%) dose reduced palbociclib from 125 mg to 100 mg as their preferred method of dose modification, while others dose reduced from 125 mg to 75 mg (10.5%) and altered the schedule to 125 mg every other day (7.9%). A comparable rate of palbociclib dose modifications and subsequent dose changes were identified in an age ≥ 65 subgroup. In this group, dose adjustments were most commonly from grade 3–4 neutropenia, occurred mainly during cycle 1, and were most frequently addressed by dose reduction from 125 to 100 mg.ConclusionsNeutropenia remains the predominant cause for palbociclib dose modification and most modifications occur within the first two cycles. Older age (≥ 65) does not affect palbociclib tolerance. Our findings provide context outside of a clinical trial that inform ongoing studies evaluating the safety and feasibility of palbociclib-based therapies.
Highlights
In February 2015, the CDK4/6 inhibitor, palbociclib, in combination with letrozole, was approved by the FDA as first-line treatment of metastatic postmenopausal, hormone receptor (HR)-positive breast cancer
Palbociclib was initially approved on the basis of a small number of patients treated on the PALOMA 1 study
The PALOMA 2 and PALOMA 3 trials included over 700 patients and confirmed grade 3 and 4 neutropenia as the most common side effect from palbociclib and endocrine therapy [2, 3]
Summary
In February 2015, the CDK4/6 inhibitor, palbociclib, in combination with letrozole, was approved by the FDA as first-line treatment of metastatic postmenopausal, hormone receptor (HR)-positive breast cancer. The PALOMA 2 trial confirmed the favorable results of PALOMA 1 in a larger population of patients [3] These three studies established CDK4/6 inhibitors as an important class of drugs in the treatment of metastatic HR-positive/HER2-negative breast cancer. The PALOMA 2 study identified grade 3 and 4 neutropenia in 66.4% of patients receiving palbociclib and letrozole compared to 1.4% with letrozole alone [3]. In PALOMA 3, grade 3–4 AEs were more common in patients receiving palbociclib; neutropenia (65% in palbociclib + fulvestrant arm vs 1% in placebo + fulvestrant arm), leucopenia (28% vs 2%), anemia (3% vs 2%), and thrombocytopenia (3% vs 0%) [2]. Febrile neutropenia was rare and seen in only three patients receiving palbociclib + fulvestrant and one patient receiving placebo + fulvestrant
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