The main objective of the study is 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

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 by 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 four neutropenia as the most common side effect of palbociclib and endocrine therapy.

The implementation of adding palbociclib to endocrine therapy is in clinical practice from periods; myelosuppression is becoming increasingly recognized as toxicity that may lead to dose modification. Hence the study is conducted to characterize toxicities observed with palbociclib resulting in dose modifications.

Researchers 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.

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 two 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.

Neutropenia remains the predominant cause for palbociclib dose modification, and most changes occur within the first two cycles. Older age (≥ 65) does not affect palbociclib tolerance. The findings provide context outside of a clinical trial that informs ongoing studies evaluating the safety and feasibility of palbociclib-based therapies.

The present study have certain limitations because of its retrospective design. However, our data provide useful insights into the prescribing patterns of physicians while they become comfortable with the use of a new agent.