A single institution experience with palbociclib toxicity requiring dose modifications.

Abstract

PURPOSE:

Since 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.

METHODS:

We 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.

RESULTS:

From 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.

CONCLUSIONS:

Neutropenia 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.

• Authors: Jun Gong, May Cho, Kim Wai Yu, James Waisman, Yuan Yuan, Joanne Mortimer
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 168 Issue 2 Pg. 381-387 (Apr 2018) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 29218462 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Hormonal
• Piperazines
• Protein Kinase Inhibitors
• Pyridines
• Receptors, Estrogen
• ERBB2 protein, human
• Receptor, ErbB-2
• palbociclib

Topics

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Hormonal (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy, pathology)
• Chemotherapy-Induced Febrile Neutropenia (epidemiology, etiology)
• Dose-Response Relationship, Drug
• Female
• Humans
• Middle Aged
• Piperazines (administration & dosage, adverse effects)
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pyridines (administration & dosage, adverse effects)
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Retrospective Studies