Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2018

01-08-2018 | Clinical trial

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

Authors: G. Hoste, K. Punie, H. Wildiers, B. Beuselinck, I. Lefever, E. Van Nieuwenhuysen, S. N. Han, P. Berteloot, N. Concin, R. Salihi, I. Vergote, P. Neven

Published in: Breast Cancer Research and Treatment | Issue 1/2018

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Boér K (2016) Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer. Onco Targets Ther 9:6119–6125CrossRefPubMedPubMedCentral
2.
Maurer C, Martel S, Zardavas D, Ignatiadis M (2017) New agents for endocrine resistance in breast cancer. The Breast 34:1–11CrossRefPubMed
3.
Almstedt K, Schmidt M (2015) Targeted therapies overcoming endocrine resistance in hormone receptor-positive breast cancer. Breast Care (Basel) 10(3):168–172CrossRef
4.
Cardoso F, Costa A, Senkus E et al (2017) 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol 28(1):16–33PubMed
5.
Augereau P, Patsouris A, Bourbouloux E et al (2017) Hormonoresistance in advanced breast cancer: a new revolution in endocrine therapy. Ther Adv Med Oncol 9(5):335–346CrossRefPubMedPubMedCentral
6.
Vidula N, Rugo HS (2016) Cyclin-dependent kinase 4/6 inhibitors for the treatment of breast cancer: a review of preclinical and clinical data. Clin Breast Cancer 16(1):8–17CrossRefPubMed
7.
Turner NC, Ro J, André F et al (2015) Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med 373(3):209–219CrossRefPubMed
8.
Finn RS, Crown JP, Lang I et al (2015) The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16(1):25–35CrossRefPubMed
9.
10.
Sledge GW Jr, Toi M, Neven P et al (2017) MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35(25):2875–2884CrossRefPubMed
11.
Bilgin B, Sendur MAN, Şener Dede D, Akıncı MB, Yalçın B (2017) A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer. Curr Med Res Opin 33(9):1559–1569CrossRefPubMed
12.
Romero D (2016) Breast cancer: MONALEESA-2 and FALCON—PFS advantage. Nat Rev Clin Oncol 13(12):717CrossRefPubMed
13.
Beaver JA, Amiri-Kordestani L, Charlab R et al (2015) FDA approval: palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. Clin Cancer Res 21(21):4760–4766CrossRefPubMed
14.
Cristofanilli M, Turner NC, Bondarenko I et al (2016) Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 17(4):425–439CrossRefPubMed
15.
16.
Finn RS, Martin M, Rugo HS et al (2016) Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375(20):1925–1936CrossRefPubMed
17.
18.
Chirila C, Mitra D, Colosia A et al (2017) Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis. Curr Med Res Opin 33(8):1457–1466CrossRefPubMed
19.
Patnaik A, Rosen LS, Tolaney SM et al (2016) Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors. Cancer Discov 6(7):740–753CrossRefPubMed
20.
DeMichele A, Clark AS, Tan KS et al (2015) CDK 4/6 inhibitor palbociclib (PD0332991) in Rb + advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res 21(5):995–1001CrossRefPubMed
21.
Finn RS, Dering J, Conklin D et al (2009) PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res 11:R77CrossRefPubMedPubMedCentral
22.
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247CrossRefPubMed
23.
Iwase H, Yamamoto Y (2015) Clinical benefit of sequential use of endocrine therapies for metastatic breast cancer. Int. J Clin Oncol 20(2):253–261CrossRefPubMed
24.
Kim ES, Scott LJ. Palbociclib (2017) A review in HR-positive, HER2-negative, advanced or metastatic breast cancer. Target Oncol 12(3):373–383CrossRefPubMed
25.
Hu W, Sung T, Jessen BA et al (2016) Mechanistic investigation of bone marrow suppression associated with palbociclib and its differentiation from cytotoxic chemotherapies. Clin Cancer Res 22(8):2000–2008CrossRefPubMed
26.
Rugo HS (2016) Dosing and safety implications for oncologists when administering everolimus to patients with hormone receptor-positive breast cancer. Clin Breast Cancer 16(1):18–22CrossRefPubMed
27.
Fribbens C, O’Leary B, Kilburn L et al (2016) Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol 34(25):2961–2968CrossRefPubMed
28.
Shah AN, Cristofanilli M (2017) The growing role of CDK4/6 inhibitors in treating hormone receptor-positive advanced breast cancer. Curr Treat Options Oncol 18(1):6CrossRefPubMed
29.
O’Leary B, Hrebien S, Morden JP et al (2018) Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. Nat Commun 9(1):896CrossRefPubMedPubMedCentral
Metadata
Title
Palbociclib in highly pretreated metastatic ER-positive HER2-negative breast cancer
Authors
G. Hoste
K. Punie
H. Wildiers
B. Beuselinck
I. Lefever
E. Van Nieuwenhuysen
S. N. Han
P. Berteloot
N. Concin
R. Salihi
I. Vergote
P. Neven
Publication date
01-08-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4827-6

Other articles of this Issue 1/2018

Breast Cancer Research and Treatment 1/2018 Go to the issue

Epidemiology

Predictors of surveillance mammography outcomes in women with a personal history of breast cancer

Epidemiology

Associations of dietary intake and supplement use with post-therapy cognitive recovery in breast cancer survivors

Review

Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG)

Epidemiology

Uptake of BRCA 1/2 and oncotype DX testing by medical and surgical oncologists

Letter to the Editor

Tamoxifen-induced fatty liver disease in a Caucasian patient

Preclinical study

Construction of a novel multi-gene assay (42-gene classifier) for prediction of late recurrence in ER-positive breast cancer patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits