scholarly journals Ribociclib in the treatment of HR+ HER2-negative metastatic breast cancer: updated results from the randomized clinical trials and their role in the clinical practice

2021 ◽  
Vol 17 (2) ◽  
pp. 58-67
Author(s):  
I. V. Kolyadina
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Randomized Trials ◽  
Randomized Clinical Trials ◽  
Metastatic Breast ◽  
Premenopausal Women ◽  
Progression Free Survival ◽  
Free Survival ◽  
Combined Endocrine Therapy

The luminal HER2-negative subtype is the dominant variant of metastatic breast cancer; modern combined endocrine therapy with CDK4/6 inhibitors due to significantly change the prognosis of the disease, not only for increasing progression free survival, but also for significantly prolonging the life expectancy of patients. This review presents the features of the mechanism of action of CDK4/6 inhibitors, the most significant and updated results of large, randomized trials with ribociclib (MONALEESA-2, MONALEESA-3, and MONALEESA-7) assessing the efficacy and safety of combined endocrine therapy with various endocrine partners in a population of premenopausal women and menopausal patients. The prospects for the use of CDK4/6 inhibitors for therapy patients with visceral crisis are shown.

Systematic review and meta-analysis of post-progression outcomes in ER+/HER2- metastatic breast cancer after treatment with endocrine therapy and CDK 4/6 inhibitors within randomized clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1059-1059
Author(s):  
Elisabetta Munzone ◽  
Eleonora Pagan ◽  
Vincenzo Bagnardi ◽  
Emilia Montagna ◽  
Giuseppe Cancello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Fixed Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Progression Free Survival

1059 Background: CDK4/6 inhibitors combined with endocrine therapy (ET) deeply transformed the treatment landscape of HR+/HER2− advanced breast cancer. After progression with the combination, there are no established guidelines for an optimal sequencing of the various therapeutic options. Data from randomized clinical trials (RCT) suggest that subsequent progression free survival (PFS2) was not compromised by the use of these drugs and time to subsequent chemotherapy (TTC) may be delayed. Therefore, we performed a meta-analysis to evaluate the benefit of such treatments on PFS2 and on delaying the TTC. Methods: We conducted a systematic literature search using PubMed to select all available randomized clinical trials of CDK4/6-inhibitors and ET reporting PFS2 or TTC data in first- or second-line therapy of HR+/HER2- pre- or postmenopausal metastatic breast cancer. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled hazard ratios (HR) for PFS2 and TTC with 95% confidence intervals (CI) using fixed-effects models. The pooled HRs for PFS and OS were also calculated. I2 was used to quantify heterogeneity between studies’ results. Results: Seven studies (PALOMA 1-2-3, MONALEESA 3-7, MONARCH 2-3) were included in our analyses (n = 3912 patients). A clear PFS2 benefit was observed in patients who received CDK 4/6 inhibitors + ET (pooled HR = 0.67, 95% CI = 0.61 to 0.74, I2 = 0.0%) and also a delay in subsequent TTC (pooled HR = 0.63, 95% CI = 0.58 to 0.70, I2 = 0.0%). As previously reported, the benefit in terms of PFS (pooled HR = 0.54, 95% CI = 0.50 to 0.59, I2= 0%) and OS (pooled HR = 0.77, 95% CI = 0.68 to 0.86, I2= 0%) was also confirmed. Conclusions: CDK4/6-inhibitors plus ET compared with ET alone improve PFS2, and TTC. The delay of chemotherapy can spare the patients toxicities, potentially improving the quality of life. Thus, the observed benefit in PFS2 may postpone the onset of endocrine resistance and may offer an additional therapeutic advantage in this setting.

scholarly journals Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 21 (17) ◽  
pp. 6400 ◽  
Author(s):  
Michela Piezzo ◽  
Paolo Chiodini ◽  
Maria Riemma ◽  
Stefania Cocco ◽  
Roberta Caputo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Meta Analysis ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Sites

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).

Real-world survival data of palbociclib in advanced and metastatic breast cancer: A multicenter experience in Lebanon.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13054-e13054
Author(s):  
Lewis Nasr ◽  
Ahmad Ghoche ◽  
Saada Diab ◽  
Fadi Nasr
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Endocrine Therapy ◽  
Real World ◽  
De Novo ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Visceral Metastasis ◽  
Free Survival

e13054 Background: Approximately 70% of all breast cancer cases are hormone receptor (HR) positive. One of the most important treatment strategies for HR positive, human epidermal growth factor receptor 2 (HER2) negative subtype was endocrine treatment monotherapy by targeting estrogen receptor or aromatization and thus reducing estrogen level. However, resistance to this treatment and disease progression is universal. In the past few years, palbociclib, an oral inhibitor of cyclin dependent kinase 4 and 6 have been approved by the FDA, as a new standard of care in the metastatic or locally advanced setting either as front line therapy or after progression. The aim of our study is to describe the real world experience with palbociclib. Methods: Eligible patients had histologically confirmed metastatic breast cancer estrogen and progesterone receptors positive and HER2 receptor negative. Palbociclib was given 125 mg orally for 21 consecutive days of a 28 day cycle. Patients were followed over one year. Primary objective was progression free survival (PFS). Tumor response and treatment tolerability were defined as secondary objectives. Results: From 2002 to 2018, we identified a total of 44 breast cancer patients. All patients were females. The median age at diagnosis was 57 years. Among all the patients, 33.3% had visceral metastasis, 35.9% had non visceral metastasis and 30.8% had the two types of metastasis. 64.1% were de novo metastatic and 35.9% were not de novo metastatic. 82.5% had less than 3 sites of metastasis. 47% of the study patients had received both chemotherapy and endocrine therapy during treatment course, and 13 % had only received prior adjuvant endocrine therapy. 28.26% took only prior systemic therapy for breast cancer. By the cutoff date for the final analysis (1/11/2018), a total of 8 events of disease progression occurred, no death events happened. The median progression free survival was 262.6 months for palbociclib combined with letrozole as first line. Conclusions: no data was published before on palbociclib in Lebanon. We are the first to describe these characteristics. Our result (PFS 26 2.6 months) is in conformity with the PFS obtain with PALOMA-2 (24 months).

scholarly journals Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer

2020 ◽  
Vol 16 (33) ◽  
pp. 2763-2778
Author(s):  
Miguel Martin ◽  
Jose A Garcia-Saenz ◽  
Luis Manso ◽  
Antonio Llombart ◽  
Alejo Cassinello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Objective Response ◽  
Metastatic Breast ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
First Line ◽  
Free Survival

The addition of CDK4 and 6 inhibitors (abemaciclib, palbociclib or ribociclib) to endocrine therapy, as first-line treatment or following progression after initial endocrine therapy, significantly increased progression-free survival, objective response rates and in some trials overall survival, compared with endocrine therapy alone in HR+ and HER2- breast metastatic breast cancer. These CDK4 and 6 inhibitors are now approved in this context and have become a new standard of care. A hypothesis-generating exploratory analysis suggested that the addition of abemaciclib to endocrine therapy showed the largest effects in subgroups of women with indicators of poor prognosis, although these data require confirmation. This review provides updated clinical trial data for all three drugs in metastatic breast cancer, focusing on abemaciclib, the most recently approved agent.

scholarly journals Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

2021 ◽  
Author(s):  
Pavani Chalasani ◽  
Kiah Farr ◽  
Vicky Wu ◽  
Isaac Jenkins ◽  
Alex Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Peripheral Neuropathy ◽  
Clinical Benefit ◽  
Low Dose ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

scholarly journals Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Raffaella Palumbo ◽  
Rosalba Torrisi ◽  
Federico Sottotetti ◽  
Daniele Presti ◽  
Anna Rita Gambaro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Receptor ◽  
Treatment Line ◽  
Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

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