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.

Duration of Chemotherapy for Metastatic Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

2011 ◽  
Vol 29 (16) ◽  
pp. 2144-2149 ◽  
Author(s):  
Alessandra Gennari ◽  
Martin Stockler ◽  
Matteo Puntoni ◽  
Mariapia Sormani ◽  
Oriana Nanni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Published Data ◽  
First Line ◽  
Line Chemotherapy

Purpose To evaluate the effect of different first-line chemotherapy durations in patients with metastatic breast cancer (MBC) on overall survival (OS) and progression-free survival (PFS). Methods We searched literature databases to identify randomized controlled trials that compared different chemotherapy durations in the first-line treatment of MBC. Only trials with unconfounded comparisons of additional cycles of chemotherapy were included. The main outcome measures for this analysis were OS and PFS. Published data from retrieved studies were analyzed according to standard meta-analytic techniques. Results We found 11 randomized clinical trials including 2,269 patients. Longer first-line chemotherapy duration resulted into a significantly improved OS (hazard ratio [HR], 0.91; 95% CI, 0.84 to 0.99; P = .046) and PFS (HR, 0.64; 95% CI, 0.55 to 0.76; P < .001). There were no differences in effects on either OS or PFS between subgroups defined by time of random assignment, study design, number of chemotherapy cycles in the control arm or concomitant endocrine therapy. Conclusion Longer first-line chemotherapy duration is associated with marginally longer OS and a substantially longer PFS.

scholarly journals Role of nab-paclitaxel in metastatic breast cancer: a meta-analysis of randomized clinical trials

Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 72950-72958 ◽  
Author(s):  
Yun Liu ◽  
Guoxin Ye ◽  
Dali Yan ◽  
Lei Zhang ◽  
Fan Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Metastatic Breast

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.

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]).

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 Bevacizumab and Breast Cancer: A Meta-Analysis of First-Line Phase III Studies and a Critical Reappraisal of Available Evidence

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
José R. Rossari ◽  
Otto Metzger-Filho ◽  
Marianne Paesmans ◽  
Kamal S. Saini ◽  
Alessandra Gennari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Statistical Estimates ◽  
Treatment Indications ◽  
Phase Iii Studies

Background. Randomized studies have shown different magnitude of bevacizumab benefit in the treatment of advanced breast cancer. Regulatory agencies have modified bevacizumab treatment indications across different regions. In this study, we perform a meta-analysis of phase III studies aiming to interrogate the magnitude of bevacizumab benefit for the treatment of first-line HER2-negative metastatic breast cancer (MBC).Methods. Data from studies E2100, AVADO and RIBBON-1 were used to calculate the benefit of bevacizumab in terms of tumor overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Combined statistical estimates of hazard ratios (HR) and odds ratios were calculated using fixed-effects or random-effects models.Results. A total of 2,695 patients were evaluated. Combining bevacizumab with different chemotherapy backbones resulted in a 30% risk reduction of PFS events (HR = 0.70; 95% confidence interval [CI], 0.57–0.86) and increased ORR (odds ratio 1.81; 95% CI, 1.53–2.14). No OS benefit could be demonstrated (HR = 0.95; 95% CI, 0.85–1.06). Bevacizumab significantly increased the incidence of adverse events such as proteinuria, hypertension and cardiovascular events.Conclusions. Bevacizumab combined with chemotherapy in the first-line treatment of MBC significantly improved ORR and PFS, but also increased grade 3-4 toxicities. No significant OS advantage was observed.

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