Abstract P1-16-01: Efficacy of endocrine- versus chemotherapy-based treatments in hormone receptor-positive (HR+ve), HER2-negative (HER2-ve) postmenopausal metastatic breast cancer (mBC): A network meta-analysis (NMA)

2019 ◽  
Author(s):  
F Schettini ◽  
M Giuliano ◽  
C Rognoni ◽  
S De Placido ◽  
G Arpino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Hormone Receptor Positive

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.

A network meta-analysis of fulvestrant vs alternative first-line endocrine therapies for endocrine therapy-naive postmenopausal hormone receptor-positive advanced or metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12545-e12545 ◽  
Author(s):  
Claire Telford ◽  
Shweta Takyar ◽  
Parth Joshi ◽  
Mattias Ekman ◽  
Nick Jones
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Proportional Hazards ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
First Line ◽  
Hormone Receptor Positive ◽  
American Society

e12545 Background: Fulvestrant (F) is a selective estrogen degrader for hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (LA/MBC). This network meta-analysis examined the efficacy of F (500 mg) vs alternative endocrine therapies (ETs) for first-line treatment of ET-naïve HR+ LA/MBC. Methods: Randomized controlled trials of first-line F, tamoxifen (Tam), anastrozole (A), exemestane (E), letrozole (L), and toremifene (T) for women (≥18 years) with HR+ LA/MBC and no prior ET were identified in a systematic review of MEDLINE, EMBASE, and Cochrane databases from inception to October 2016. Conference proceedings of the American Society of Clinical Oncology, European Society of Medical Oncology, and San Antonio Breast Cancer Symposium from 2013-2016 were hand searched. Trials of targeted combination therapies were excluded. Studies were checked for heterogeneity. A standard fixed-effect Bayesian network meta-analysis was conducted based on hazard ratios (HRs) and assuming proportional hazards for progression-free and overall survival (PFS/OS). Results: Seven eligible studies (1 Phase [Ph] 2, 5 Ph 3, 1 Ph 2/3) were identified. All had PFS data; five had OS data. Two trials compared F vs A; PFS data were available for both trials; sufficiently mature OS data for F were available from Ph 2 only. The proportional hazards assumption was met for PFS only.F had significantly improved PFS vs Tam (HR 0.57, 95% credibility interval [Crl] 0.44-0.73), A (HR 0.75, 95% Crl 0.62-0.91), E (HR 0.65, 95% Crl 0.47-0.91), and T (HR 0.53, 95% Crl 0.37-0.78). Numerically improved PFS was observed for F vs L (HR 0.81, 95% Crl 0.59-1.11). F had significantly improved OS vs Tam (HR 0.63, 95% Crl 0.40-0.98), A (HR 0.63, 95% Crl 0.42-0.94), and E (HR 0.56, 95% Crl 0.33-0.95). OS was numerically improved with F vs L (HR 0.66, 95% Crl 0.41-1.04). Conclusions: This analysis suggests improved PFS and OS for fulvestrant vs tamoxifen, anastrozole, exemestane, and letrozole, and PFS for fulvestrant vs toremifene. Further analysis should be conducted, using non-proportional hazard methods and more mature OS data, to confirm the OS results.

Ranking of therapeutic regimens for hormone receptor-positive, HER2-negative, metastatic breast cancer (MBC) using information theoretic network meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2050-2050
Author(s):  
Xuanyi Li ◽  
Hossein Tavana ◽  
Suresh Bhavnani ◽  
Jeremy Lyle Warner
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Targeted Therapy ◽  
Hormone Therapy ◽  
Hormone Receptor ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Information Theoretic ◽  
Hormone Receptor Positive ◽  
Over Time

2050 Background: Hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) is treated with targeted therapy, hormone therapy, chemotherapy, or combinations of these modalities. Evaluating the increasing number of treatment options is challenging, especially since few regimens have been compared head-to-head in randomized clinical trials (RCTs). Potential solutions include expert-driven guidelines (e.g. NCCN guidelines), algorithmic scales (e.g. the ASCO and ESMO Value Frameworks), traditional Bayesian network meta-analysis (NMA), and information theoretic (IT) NMA, a graph theory-based approach that also enables dynamic ranking of regimens over time. Methods: We used IT-NMA to rank regimens for HR+/HER2- MBC. The analysis includes RCTs of regimens identified from HemOnc.org and a recent large traditional NMA (Giuliano et al. 2019). Variables used in ranking include primary endpoints, no. of patients enrolled, p-value, hazard ratio for time-based outcomes (e.g. overall survival) or odds ratio for fixed endpoints (e.g. response rate), and year of publication. Results: The analysis included 238 RCTs enrolling 92,971 patients published between 1974-2019. There were 277 unique regimens, taking into account variations in dosage, frequency, and no. of cycles. As of 2019, out of 85 ranks, combinations of targeted therapy and hormone therapy (e.g. letrozole & palbociclib) are ranked the highest (Table). Over time, we observe that novel treatments tested in escalation trials tend to rise to the top of the rankings (e.g. paclitaxel & bevacizumab in 2007, driven by ECOG E2100), and monotherapy approaches tend to fall to the bottom. Conclusions: In 2019, the combinations of hormone or chemotherapy and targeted therapy are ranked higher than hormone therapy or chemotherapy alone. Our ranking result is similar to previous studies with a notably larger number of comparisons (Giuliano et al. is the largest published study, with 131 regimens/50,029 pts analyzed). Informatic theoretic NMA is a promising method of indirect rankings of treatment that also enables dynamic regimen ranking over time. [Table: see text]

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