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Palbociclib in highly pretreated metastatic ER-positive HER2-negative breast cancer

G Hoste¹, K Punie², H Wildiers²

¹Multidisciplinary Breast Center, UZ Leuven, Herestraat 49, 3000, Leuven, Belgium. griet.hoste@uzleuven.be.

Breast Cancer Research and Treatment

|May 17, 2018

Abstract

Purpose:

We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC).

Methods:

Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment. The efficacy and safety analysis was performed in 82 patients who had received at least one dose of palbociclib and who had at least 6-month follow-up at the data cut-off point. The primary objective was the evaluation of efficacy of the combination of palbociclib and endocrine therapy with clinical benefit as primary endpoint, defined as the absence of progressive disease and being on treatment for at least 6 months. Secondary objectives were the evaluation of toxicity and the identification of potential predictors for clinical benefit.

Results:

The median age of the patients was 67.1 years (range 34.8-85.9) at the time of inclusion. The average duration of treatment was 5.6 months (range 1-19), with a median progression-free survival of 3.17 (95% CI 2.76-4.70) months. At the data cut-off point, 10 patients were still on treatment with palbociclib. In this highly pretreated setting, 34 patients experienced no progressive disease within 6 months, resulting in an overall clinical benefit rate (CBR) of 41.5%. 20.7% (17/82) showed stable disease for ≥ 9 months and 13.4% for ≥ 12 months. None of the investigated predicting factors were significantly associated with clinical benefit at 6 months. For 43.9% of the patients, treatment delay or dose reduction was indicated.

Conclusions:

Palbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.

Insights

Palbociclib combined with endocrine therapy demonstrated a 41.5% clinical benefit rate in heavily pretreated metastatic breast cancer patients. This combination showed a favorable safety profile, offering a new option for endocrine therapy-resistant cases.

Area of Science:

Oncology
Pharmacology

Background:

Metastatic breast cancer (MBC) that is resistant to endocrine therapy poses a significant clinical challenge.
Postmenopausal women with heavily pretreated, endocrine-resistant MBC have limited treatment options.

Purpose of the Study:

To evaluate the efficacy and safety of palbociclib, a cyclin-dependent kinase 4 and 6 inhibitor, in combination with endocrine therapy.
To assess palbociclib's role in postmenopausal women with highly pretreated, endocrine-resistant, estrogen receptor-positive, HER2-negative MBC.

Main Methods:

A compassionate use program included 82 postmenopausal women with advanced MBC after at least four prior systemic treatments.
Efficacy was assessed by clinical benefit rate (CBR) at 6 months; safety and predictors of benefit were also evaluated.
Patients received palbociclib plus endocrine therapy, with analysis of those receiving at least one dose and having 6-month follow-up.

Main Results:

The median progression-free survival was 3.17 months.
A clinical benefit rate (no progressive disease at 6 months) of 41.5% was observed.
Treatment was associated with dose modifications in 43.9% of patients, but demonstrated a favorable safety profile.

Conclusions:

Palbociclib combined with endocrine therapy shows a high clinical benefit rate in heavily pretreated, endocrine-resistant MBC.
The combination exhibits a favorable safety profile, suggesting it is a viable treatment option for this patient population.
Further investigation into predictive factors for palbociclib benefit in MBC is warranted.

Read full analysis

Keywords:

Compassionate use program Highly pretreated metastatic breast cancer Palbociclib

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