scholarly journals Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer

Breast Care ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. 167-173 ◽  
Author(s):  
Romualdo Barroso-Sousa ◽  
Geoffrey I. Shapiro ◽  
Sara M. Tolaney
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Clinical Development ◽  
New Drugs ◽  
Future Directions ◽  
Free Survival ◽  
Cyclin Dependent Kinases ◽  
Hormone Receptor Positive ◽  
Central Nervous System Penetration

Clinical and preclinical data support a significant role for inhibitors of the cyclin-dependent kinases (CDKs) 4 and 6 in the treatment of patients with breast cancer. Recently, based on data showing improvement in progression-free survival, the use of palbociclib (Ibrance; Pfizer, Inc.) in combination with endocrine agents was approved to treat patients with hormone receptor-positive advanced disease. Importantly, 2 other CDK4/6 inhibitors, abemaciclib (LY2835219; Lilly) and ribociclib (LEE011; Novartis), are in the late stage of clinical development. In this review, we will focus on clinical data on these 2 new drugs, highlighting their differences compared to palbociclib in terms of single-agent activity, central nervous system penetration, and common adverse events. In addition, we will present the ongoing clinical trials and discuss future directions in the field.

scholarly journals Treatment of Advanced Hormone Receptor-Positive (HR+) HER2-negative Breast Cancer

2019 ◽  
Vol 79 (12) ◽  
pp. 1328-1335
Author(s):  
Nina Ditsch ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Treatment Options ◽  
Clinical Status ◽  
Progression Free Survival ◽  
Current Treatment ◽  
Free Survival ◽  
Cyclin Dependent Kinases ◽  
Hormone Receptor Positive ◽  
Study Results

AbstractThe article gives an overview of current treatment options for metastatic hormone receptor-positive and HER2-negative breast cancer. The focus is on combined therapies, e.g., with CDK4/6 inhibition compared with purely endocrine-based therapies in the pre- and postmenopause, presenting the latest study results. The addition of a CDK4/6 inhibitor to endocrine-based therapy with an aromatase inhibitor or fulvestrant leads to a marked improvement in progression-free survival and is independently beneficial whether palbociclib, ribociclib or abemaciclib is involved. The particular clinical status of inhibition of cyclin-dependent kinases argues for its use in the first-line treatment of women with metastatic, hormone receptor-positive and HER2-negative breast cancer compared with the available purely endocrine-based therapies.

Common AEs associated with CDK4/6 inhibitors in patients with hormone receptor–positive advanced breast cancer.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 239-239
Author(s):  
Denise A. Yardley
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Safety Profile ◽  
Progression Free Survival ◽  
Well Being ◽  
Advanced Breast ◽  
Free Survival ◽  
Cyclin Dependent Kinases ◽  
Hormone Receptor Positive ◽  
Grade 3

239 Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with letrozole or fulvestrant substantially prolong progression-free survival (PFS) with a well-tolerated, predictable safety profile. Understanding the safety profile of selective CDK4/6 inhibitors can inform adverse event (AE) management and can extend and maintain time on treatment. Here, we report common AEs associated with CDK4/6 inhibitors and perspectives on monitoring as well as managing these AEs. Methods: We reviewed 5 published Phase II/III trials of ≥50 patients with advanced breast cancer (ABC) treated with CDK4/6 inhibitors in combination with endocrine therapy with respect to commonly reported AEs, defined as AEs reported in ≥15% (any grade) or ≥5% (Grade 3/4) of patients in ≥4 of 5 trials. Results: The most common AEs consisted of hematologic, gastrointestinal, and general well-being AEs (Table). Nonhematologic AEs were mostly Grade ≤2 and easily managed with dose modification. Uncomplicated neutropenia was the most common hematologic AE and was noncumulative, with the lowest neutrophil counts typically reached within a month of initiating treatment, and did not require intervention. Median time to resolution of Grade 3 neutropenia was 7–15 days. Febrile neutropenia was rare (<2%). Conclusions: CDK4/6 inhibitors are characterized by early, predictable, easily managed, transient AEs that do not require intervention. Awareness of and patient support for these AEs can enable patients with ABC to remain on CDK4/6 treatment and achieve associated PFS benefits. [Table: see text]

scholarly journals Epirubicin and docetaxel as neoadjuvant treatment of hormone receptor positive, HER-2 negative breast cancer: findings from two successive phase II studies

2013 ◽  
Vol 47 (1) ◽  
pp. 57-62
Author(s):  
Alessandro Tuzi ◽  
Davide Lombardi ◽  
Diana Crivellari ◽  
Loredana Militello ◽  
Tiziana Perin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Progression Free Survival ◽  
Preoperative Treatment ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
In Series ◽  
Her 2

Abstract Background. We report on the activity of the combination of epirubicin and docetaxel given in neoadjuvant setting for 4 and 8 cycles respectively in 2 successive series of patients with large operable or locally advanced, hormone receptor positive, HER-2 negative breast cancer. Patients and methods. Patients were treated from 2002 to 2006 with epirubicin 90 mg/m2 and docetaxel 75 mg/ m2 intravenously, every 3 weeks for 4 cycles before and 4 cycles after surgery (Series I - 13 patients), and from 2006 to 2010 with the same regimen administered for 8 cycles preoperatively (Series II - 37 patients), plus hormonal therapy for 5 years and radiation therapy if indicated. All Series I and 32 Series II patients were able to complete the preoperative chemotherapy. Results. A complete response was found in 1 patient from Series I and 13 patients from Series II and the partial remission in 10 patients from Series I and 21 patients from Series II. Two Series I and 3 Series II patients did not respond clinically. Response rate (Series I/Series II) was 84/92%. All 50 patients underwent surgery. In Series I patients, 3 pCR occurred in the breast and the axilla was histologically negative in 2 cases. No evidence of disease both in the breast and in the axilla was achieved in 7.6% (1/13) of patients. In Series II patients, 8 pCR occurred in the breast and axilla was histologically negative in 15 patients. No evidence of disease both in the breast and in the axilla occurred in 10.8% (4/37) of patients. G3-G4 toxicity included myelosuppression in 3 patients from Series I and all patients from Series II, and mucositis in 1 patient from Series I and 4 patients from series II. No other G3-4 toxicities or toxic deaths occurred. Five-year progression free survival was 38% and 90% in Series I and Series II patients respectively. Conclusions. The incidence of pathologic complete remissions was lower in our patient population, compared to reported data. A longer duration of the preoperative treatment might be associated with a longer progression-free survival.

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

2020 ◽  
Vol 20 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Jonathan Wilkie ◽  
M. Alexandra Schickli ◽  
Michael J. Berger ◽  
Maryam Lustberg ◽  
Raquel Reinbolt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hormone Receptor Positive

A phase II trial of trabectedin (T) in patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to xeroderma pigmentosum gene (XPG) expression.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS652-TPS652
Author(s):  
Ahmad Awada ◽  
Javier Cortes ◽  
Miguel Martin ◽  
Philippe Aftimos ◽  
Mafalda Oliveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Hormone Receptor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Open Label ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

TPS652 Background: Hormone receptor-positive, HER2-negative breast cancer (BC) is currently associated with 3-4 years overall survival in the metastatic setting and, after ≥2 relapses, therapeutic approaches are reduced. XPG expression is frequently modified in BC. T is a cytotoxic agent that forms a complex with the XPG, inducing cell apoptosis. As a single agent, T has shown anti-tumor activity in patients with poor prognosis BC, and a better response to T in BC patients with XPG RNA overexpression has been observed. Methods: This is an open-label, phase II study of T (1.3 mg/m2 in 3-hour intravenous infusion every 3 weeks) in patients with hormone receptor-positive, HER2-negative advanced BC, according to their primary tumor’s XPG expression. Primary endpoint: to evaluate the efficacy of T in terms of progression free survival rate at 4 months (PFS4) according to the patient’s XPG expression. Secondary endpoints: Comparison of PFS, overall response rate, duration of response, overall survival and safety profile in XPG-high and XPG-low patients. Assignment: BC patients who have previously received anthracyclins and/or taxanes and who progressed after 2-5 chemotherapy lines will be assigned according to their XPG expression from paraffin embedded tumor samples to stratum A (XPG-high [>3]) or to stratum B (XPG-low [≤3]) (threshold was selected from median XPG expression values observed in a previous trial). Statistical methods: A two-stage design was chosen: at a first stage 20 patients will be enrolled in each stratum. A futility analysis (O’Brien Fleming boundary) based on the primary endpoint (PFS4) will be conducted once 40 evaluable patients have been recruited. If ≥ 7 out of 20 patients achieve PFS4, recruitment will continue to a maximum sample size of 50 evaluable patients per stratum. If ≥ 22 out of 50 patients achieve PFS4, T will be considered active in this group (alpha error: 0.025, power: 80%). To date, 35 patients (16 XPG-high and 15 XPG-low) have been enrolled from three countries and five centers. Recruitment is ongoing.

Outcomes of talazoparib (TALA) versus physician's choice of chemotherapy (PCT) in patients (pts) with advanced breast cancer (ABC) and a germline BRCA (gBRCA) mutation by line of chemotherapy (CT) in the EMBRACA trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1071-1071
Author(s):  
Johannes Ettl ◽  
Sara A. Hurvitz ◽  
Hope S. Rugo ◽  
Kyung-Hun Lee ◽  
Lida A. Mina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
The Us ◽  
Intent To Treat

1071 Background: The PARP inhibitor TALA was approved in the US for treatment of g BRCA-mutated ABC based in part on the EMBRACA study. Understanding the outcomes of EMBRACA pts relative to prior CT is a current unmet need. Methods: EMBRACA was a randomized Phase 3 trial comparing TALA 1 mg daily vs PCT (capecitabine, eribulin, gemcitabine, vinorelbine) in g BRCA-mutated ABC. Clinical outcomes were assessed by line of prior CT for ABC in intent-to-treat (ITT), triple-negative breast cancer (TNBC), and hormone receptor-positive (HR+) breast cancer cohorts. Results: 431 pts were randomized (ITT; TALA 287; PCT: 144). TALA was generally more effective than PCT across efficacy endpoints regardless of line of CT (Table). For the ITT population, TALA improved progression-free survival (PFS) and objective response rate (ORR) vs PCT for each line of CT assessed. Other prespecified subgroups (TNBC and HR+) will be presented. Conclusions: In pts with g BRCA-mutated ABC, TALA demonstrated improvements in clinical outcomes compared with PCT regardless of prior lines of CT. Clinical trial information: NCT01945775. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document