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 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]).

Meta-analysis of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy versus endocrine therapy alone on progression-free survival (PFS) and overall survival (OS) for metastatic breast cancer (MBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1060-1060
Author(s):  
Ranju Kunwor ◽  
Ramkaji Baniya ◽  
Maysa M. Abu-Khalaf
Keyword(s):  
Endocrine Therapy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Hormone Receptor Positive

1060 Background: CDK 4/6 inhibitors with Endocrine therapy (ET) are the preferred first line treatment for Hormone Receptor positive and Human Epidermal Growth factor receptor 2 negative (HR+/HER2-) MBC. Over the last few years multiple trials have shown benefit in PFS. Only two studies evaluating Ribociclib and Abemaciclib showed an OS benefit while no statistically significant OS benefit has been reported in any of the studies evaluating Palbociclib raising the possibility that this benefit may be drug specific rather than applicable to all CDK 4/6 Inhibitors. This updated meta-analysis of randomized controlled trials (RCTs) aims to assess the PFS and OS of all three CDK 4/6 inhibitors in HR+/HER2- MBC. Methods: We performed a systematic search for RCTs using Cochrane Library, PubMed, Embase, and Web of Science. Only the phase II and III RCTs comparing CKD 4/6 inhibitors plus ET with ET alone were eligible for this meta-analysis. The pooled analysis of Hazard Ratio (HR) was performed with Review Manager 5.3 using random effect model. Results: A total of 8 RCTs including 4338 patients with HR+/HER2- MBC were included in this meta-analysis (table). The pooled HR for PFS was 0.55 (95% confidence interval (CI), 0.50-0.59; P < .00001) and the pooled HR for OS was 0.75 (95% CI, 0.68-0.84; P < .00001). Conclusions: The result of our meta-analysis confirms the previously reported PFS benefit from CDK 4/6 inhibitors plus ET and shows an OS benefit when including RCTs of all 3 CDK 4/6 inhibitors for the treatment of HR+/HER2- MBC. [Table: see text]

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.

Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2– Metastatic Breast Cancer Patients: What Is the Better Choice?

Oncology ◽  
2021 ◽  
Author(s):  
Alessandra Fabi ◽  
Mariangela Ciccarese ◽  
Sinome Scagnoli ◽  
Michelangelo Russillo ◽  
Francesco Schettini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Subsequent Treatment ◽  
Second Line ◽  
Breast Cancer Patients ◽  
Third Line ◽  
Metastatic Sites

Background: To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC). Objectives: The present study assesses, in a real-world setting, the activity of different subsequent therapies in patients who experienced a PD on palbociclib (P) + endocrine therapy (ET), to evaluate the best therapy sequence. Methods: This is a multicenter retrospective observational study. Records of consecutive HR+/HER2- MBC patients from January 2017 to May 2019 were reviewed. The primary endpoint was the evaluation of progression-free survival (PFS) according to subsequent treatment lines after progression on P+ET. Toxicity data were also collected. Results: The outcomes were analyzed in 89 MBC patients that had progressed on previous P+ET: 17 patients were on hormone therapy (HT) and 31 patients on chemotherapy (CT) as second-line treatments; seven patients were on HT and 34 on CT as third-line therapies. PFS of patients treated with HT as second-line therapy is significantly improved when compared with patients treated with CT (p=0.01). Considering third-line settings, the difference in PFS was not statistically different between HT and CT. A better outcome in terms of toxicity is observed among HT patients for both second- and third-line therapies. Conclusions: patients who were progressive on P+ET could still benefit from a subsequent ET. In patients who experienced a good efficacy from prior ET, without visceral metastatic sites, HT seems the most suitable option, when compared to CT, also in terms of safety.

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.

Endocrine therapy-based strategies with different endocrine sensitivity statuses for hormone receptor positive/HER2 negative metastatic breast cancer: A network meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1062-1062
Author(s):  
Jiani Wang ◽  
Yiqun Han ◽  
Jiayu Wang ◽  
Binghe Xu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Therapy Resistance ◽  
Optimal Treatment ◽  
Hormone Receptor Positive ◽  
Direct Head

1062 Background: Novel endocrine therapies (ETs) and targeted therapeutic regimens have been developed to dramatically improve the outcome of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Since the absence of direct head-to-head comparisons for all regimens, decision-making guidelines are urgently needed for different endocrine sensitivity statuses. This study is to evaluate the efficacy of ET-based regimens in patients with HR+/HER2- MBC and to assess the heterogeneity among different compounds with a particular focus on their ability to improve survival outcomes. Methods: This network meta-analysis of phase II/III randomized controlled trials (RCTs) with at least one ET in HR+/HER2- MBC were enrolled. Based on the endocrine responses, participants were stratified into endocrine therapy sensitivity (ETS) and endocrine therapy resistance (ETR) groups. Primary endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed by bayesian algorithms and primarily measured as surface under the cumulative ranking curve (SUCRA). Results: A total of 42 trials (22917 patients) were included. Regarding PFS, cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) +fulvestrant 500mg (F500) was recommended for the ETS group (SUCRA = 76.92%), while chemotherapy was considered as the most effective option for the ETR group (SUCRA = 73.47%). For visceral metastases, CDK4/6i +aromatase inhibitors (AIs) could provide the extreme efficacy for the ETS group (SUCRA = 63.27%) while the CDK4/6i +F500 (SUCRA = 76.17%) as the prior regimen for the ETR group. For bone-only disease, CDK4/6i+F500 was preferred for both the ETS (SUCRA = 67.04%) and the ETR (SUCRA = 70.24%) group. Concerning OS, CDK4/6i+tamoxifen was estimated as the first-rank regimen for the ETS subgroup (SUCRA = 67.04%) and chemotherapy for the ETR subgroup (SUCRA = 60.02%). Regarding resistance category, abemaciclib +F500 was likely the best option with PFS, for both primary (SUCRA = 69.19%) and secondary ETR (SUCRA = 69.09%) settings, as well as primary ETR associated with OS improvement (SUCRA = 67.67%). Pictilisib +F500 could be the optimal treatment with OS for secondary ETR (SUCRA = 60.50%)group. Conclusions: The results showed that CDK4/6i + F500 was probably the most promising option in ETS, visceral ETR and bone-only disease settings in terms of PFS. OS subgroup analysis showed that different endocrine sensitivity statuses required various optimal treatment strategies.

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.

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