The effect of everolimus on adipose tissue in patients with metastatic breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13026-e13026
Author(s):  
Ana Acuna Villaorduna ◽  
Heidi Ko ◽  
Orli Haken ◽  
June Deng ◽  
Janki Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Body Mass ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Mass Composition ◽  
Skeletal Muscle Index ◽  
Obesity And Diabetes

e13026 Background: Obesity has been associated with negative outcomes in early breast cancer. Addition of everolimus (Eve) to endocrine therapy improves progression-free survival (PFS) in patients with hormone-receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). Eve targets the mTOR signaling pathway which regulates cell growth/metabolism and has been implicated in obesity and diabetes. Changes in weight and body mass composition and its correlation with PFS have not been described in patients with MBC treated with Eve. We aim to compare total adipose tissue (TAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) before and after treatment with Eve in patients with HR+/HER2- MBC. Methods: Patients with metastatic HR+/HER2- MBC treated with Eve and endocrine therapy (Eve/ET) between 2012 and 2018 were identified. Each Eve/ET case was matched to a patient who received endocrine therapy alone (ET) by age at diagnosis (+/- 5 yrs), body mass index [BMI] (+/-5 kg/m2) and visceral metastatic disease. VAT, SAT, TAT, and skeletal muscle index (SMI) were measured by computerized tomography at L3 level using TOMOVISION software prior to treatment initiation (T0) and after 3-6 months of treatment (T3). TAT was defined as SAT + VAT and sarcopenia as SMI < 40. Paired t-test and Wilcoxon paired-test were used to compare body composition parameters at T3 vs T0 in Eve/ET and ET groups. Results: 78 patients (Eve/ET: 41 and ET: 37) with a median age of 65.5 yrs were included. Of these, 16 (21.3%) were Non-Hispanic White, 31 (41.3%) were Non-Hispanic Black and 27 (36%) were Hispanics. Visceral metastases were seen in 57 (73.1%) cases. Mean weight, BMI, VAT and SAT at T0 were 70.8 kg, 27.4 kg/m2, 170.1 cm2 and 196.1 cm2, respectively and did not differ between Eve/ET and ET groups at baseline. At T3, there was a reduction in TAT (348.4 to 289.2 cm2, p < 0.01) and SAT (181.7 to 142.7 cm2, p < 0.01) in the Eve/HT group; while there were no significant changes in TAT (373.1 to 363.9 cm2, p = 0.39) or SAT (212 to 221.8 cm2, p = 0.33) in the ET group. No changes in visceral fat %, VAT/SAT ratio and sarcopenia between T0 and T3 in either treatment group were seen. In patients treated with Eve/ET, there were no differences in PFS between low TAT-loss (TAT loss < 40 cm2) and high TAT-loss (TAT loss > 40 cm2) (3.6 vs 4.8 months, p = 0.97). Conclusions: Eve induces TAT loss in patients with HR+/HER2- MBC, specifically driven by decrease in SAT. The pathophysiology of this association is still to be discerned. Further studies are required to evaluate TAT or SAT as a predictive/prognostic biomarker in patients receiving Eve.

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.

scholarly journals Circulating Tumor Cells: A Useful Predictor of Treatment Efficacy in Metastatic Breast Cancer

2009 ◽  
Vol 27 (31) ◽  
pp. 5153-5159 ◽  
Author(s):  
Minetta C. Liu ◽  
Peter G. Shields ◽  
Robert D. Warren ◽  
Philip Cohen ◽  
Mary Wilkinson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Endocrine Therapy ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Disease Status ◽  
Radiographic Disease

PurposeFive or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging.Patients and MethodsSerial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals.ResultsSixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.ConclusionWe provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.

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 ◽  
Author(s):  
Michela Piezzo ◽  
Paolo Chiodini ◽  
Maria Riemma ◽  
Stefania Cocco ◽  
Roberta Caputo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Visceral Metastases ◽  
Metastatic Sites

Abstract PURPOSE: The introduction of CDK4/6 inhibitors plus endocrine therapy (ET) represents the most relevant advance in the management of HR-positive/HER2-negative metastatic breast cancer. We carried out a meta-analysis of randomized controlled trials (RCTs) with the aims of better characterising the efficacy of CDK4/6 inhibitors in some relevant subgroups and of testing heterogeneity between different compounds with particular focus on their ability to improve OS. METHODS: We performed a systematic literature search to identify phase II/III RCTs of CDK4/6 inhibitors plus ET in AI-sensitive and AI-resistant patients. Pooled estimates of HRs were computed for PFS, OS and ORR analysis, by using both a fixed and random effect model. Predefined subgroup analyses were performed to better understand treatment effect concerning specific patients’ characteristics. Pooled survival curves were generated by pooling the data of all trials. RESULTS: 8 RCTs were included. Adding a CDK4/6 inhibitors 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 TFI. The addition of CDK4/6 inhibitors significantly improves OS in AI-sensitive (HR 0.75, 95%CI [0.63-0.89]) 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]). CONCLUSION: Our meta-analysis confirms the efficacy of CDK4/6 inhibitors overall and in major patients subgroups, supporting the use of CDK4/6 inhibitors plus ET as standard treatment for most HR+ MBC patients.

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 Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Costanza Paoletti ◽  
Meredith M. Regan ◽  
Samuel M. Niman ◽  
Emily M. Dolce ◽  
Elizabeth P. Darga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Cell Number ◽  
Rapid Progression ◽  
Breast Cancer Patients ◽  
Er Positive

AbstractCirculating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.

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.

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]).

Sign in / Sign up

Export Citation Format

Share Document