# Palbociclib in Combination with Endocrine Therapy in Patients with Metastatic Breast Cancer in a Real-World Population: Impact of Dose-Intensity, Dose Reductions and Cycle Delays on Efficacy

## TL;DR

This study shows that lower doses of palbociclib, especially due to treatment delays, increase the risk of cancer progression in breast cancer patients.

## Contribution

The study reveals how real-world dose adjustments of palbociclib affect treatment outcomes in metastatic breast cancer patients.

## Key findings

- 35% of patients experienced dose reductions or cycle delays within six months of treatment.
- Lower dose intensity and prolonged cycle delays were strongly linked to earlier disease progression.
- Initial doses below 125 mg and six-month dose intensity under 14,250 mg increased progression risk.

## Abstract

With the addition of palbociclib to endocrine therapy, hormone receptor-positive metastatic breast cancer patients may experience toxicities leading to dose reductions and cycle delays. We examined the actual dose received during the first six months of treatment and the patient response. Records of women treated at Sainte-Catherine Institute were retrospectively reviewed anticipated dose reductions, extended cycle delays, six-month dose intensity, and treatment response were analyzed. Among 131 patients, 35% experienced an anticipated dose reduction or extended cycle delay. Logistic regression showed that anticipated dose reduction or extended cycle delay, cycle delay longer than four weeks, an initial dosage below 125 mg, and a six-month dose intensity under 14,250 mg were strongly associated with six-month progression. In this real-world study, lower palbociclib dose intensity, particularly due to prolonged cycle delays, was associated with an increased risk of early disease progression.

Purpose: With the addition of palbociclib to endocrine therapy, many hormone receptor-positive (HR+) metastatic breast cancer (mBC) patients experience toxicities that can lead to dose reductions and cycle delays. We examined the actual doses of palbociclib received by patients and their treatment responses. These dose adjustments, made at the physician’s discretion, are not always consistent with pharmaceutical company recommendations. The aim of this study was to assess the influence of dose adjustments on dose intensity and treatment response in our patients. Methods: Records of patients with HR+ mBC treated with palbociclib between December 2016 and January 2019 at the Sainte-Catherine Institute were retrospectively reviewed. Dose intensity was defined as the total dose of palbociclib received by each patient during the first six months of treatment. Anticipated dose reductions and extended cycle delays were recorded. Treatment response at six months and survival were assessed using statistical analyses. Results: A total of 131 women were included; the median age was 67 years. Forty-six patients (35%) experienced an anticipated dose reduction or an extended cycle delay during the first six months of treatment. Logistic regression analysis showed that factors correlated with six-month treatment response included anticipated dose reduction or extended cycle delay (OR = 14.6, 95% CI 3.74–97.4, p < 0.001), cycle delay > 4 weeks (OR = 5.94, 95% CI 1.58–21, p = 0.01), initial dosage < 125 mg (OR = 4.09, 95% CI 1.13–13.7, p = 0.034), and six-month dose intensity < 14,250 mg (OR = 26.0, 95% CI 4.91–481, p < 0.001). Conclusions: In this real-world assessment of clinical outcomes in French patients with HR+ mBC treated with palbociclib, a palbociclib dose intensity lower than recommended—particularly due to cycle delays longer than four weeks—was associated with an increased risk of six-month disease progression.