Dataset Information

Network Meta-Analysis of the Effectiveness of Neoadjuvant Endocrine Therapy for Postmenopausal, HR-Positive Breast Cancer.

ABSTRACT: In clinical practice, it is necessary to define an optimal choice from many different therapeutic regimens. This study aimed to assess the efficacy and safety of neoadjuvant endocrine therapy (NET) for breast cancer patients. Randomized clinical trials were included. Nine studies comprising 2133 patients were included in the final analysis. Network meta-analysis showed that everolimus plus letrozole was more easily accepted by patients than exemestane (?20wks) (odds ratio (OR): 856697.02, 95% confidence intervals (95%CI): 1.88 to 87242934...); exemestane (?20wks) had worse acceptability than letrozole (OR: 0.00, 95%CI: 0.00 to 0.98). Letrozole produced a better clinical objective response (COR) than tamoxifen (OR: 1.99, 95%CI: 1.04 to 3.80). The incidence of fatigue between the anastrozole plus gefitinib group and the everolimus plus letrozole group was significantly different (OR: 0.08, 95%CI: 0.01 to 0.83). The exemestane (<20wks) plus celecoxib group had fewer hot flushes than others. Ranking showed the everolimus plus letrozole was most likely rank first in comparisons of COR and acceptability, and had a 64% possibility to rank first after stochastic multi-criteria acceptability analysis. In conclusion, our study showed that letrozole plus everolimus is the most effective treatment for postmenopausal, hormone receptor-positive breast cancer in the neoadjuvant setting.

SUBMITTER: Wang W

PROVIDER: S-EPMC4865840 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Network Meta-Analysis of the Effectiveness of Neoadjuvant Endocrine Therapy for Postmenopausal, HR-Positive Breast Cancer.

Wang Wei W Liu Chenghao C Zhou Wenbin W Xia Tiansong T Xie Hui H Wang Shui S

Scientific reports 20160513

In clinical practice, it is necessary to define an optimal choice from many different therapeutic regimens. This study aimed to assess the efficacy and safety of neoadjuvant endocrine therapy (NET) for breast cancer patients. Randomized clinical trials were included. Nine studies comprising 2133 patients were included in the final analysis. Network meta-analysis showed that everolimus plus letrozole was more easily accepted by patients than exemestane (≥20wks) (odds ratio (OR): 856697.02, 95% co ...[more]

PMID: 27174543

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Project description:Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor-positive (HR+) tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as first-line therapy for HR+/HER- advanced BC with special consideration for the former in ET-naïve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients. Although the safety profiles of these combinations are generally predictable and manageable, both everolimus and palbociclib are associated with an increased risk of potentially serious or early-onset toxicities requiring individualized a priori adverse event risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Although each of these combinations improves progression-free survival, none with the exception of anastrazole plus fulvestrant have demonstrated improved overall survival. PI3K catalytic-? mutations assessed from circulating tumor DNA represent the first potentially viable serum biomarker for the selection of ET combinations, and new data demonstrate the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis. Therapeutic ratios of select ET combinations support their use in first- and second-line settings, but optimal sequencing has yet to be determined.2017;22:12-24 IMPLICATIONS FOR PRACTICE: Emerging data show that new endocrine therapy (ET) combinations can improve progression-free and overall survival outcomes in patients with hormone receptor-positive, HER2-negative (HR+/HER-) advanced breast cancer. Level 1 evidence supports consideration of dual ET regimens, particularly in ET-naïve patients, or palbociclib plus letrozole as first-line therapy, as well as the addition of mTOR or CDK4/6 inhibitors to established ET in the second-line setting and in select first-line patients. Some combinations are associated with increased risk of class-specific toxicities that will require individualized risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Recent data on a noninvasive biomarker assay that predicts response to a phosphoinositide 3-kinase inhibitor demonstrates the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis.

Project description:Importance:Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear. Objective:To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer. Data Sources:Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015. Study Selection:Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n?=?20). Two authors independently analyzed the studies for inclusion. Data Extraction and Synthesis:Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. Results:The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P?=?.85; n?=?378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P?=?.12; n?=?378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P?=?.07; n?=?334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P?<?.001; n?=?1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P?<?.001; n?=?1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P?<?.001; n?=?918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P?=?.03; n?=?355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P?=?.11; n?=?537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%). Conclusions and Relevance:Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.

Project description:Metastatic breast cancer (MBC) results in substantial morbidity and mortality for women afflicted with this disease. A majority of MBCs are hormone-responsive and estrogen receptor-positive, making endocrine therapy (ET) an integral component of systemic therapy. With a primary goal of minimizing the effects of estrogen on hormone-responsive MBC, ETs are among the first targeted treatments that aim to inhibit the influence of estrogen receptor activation on tumor proliferation. Several biochemical mechanisms have been the focus of drug development for treatment, including selective estrogen-receptor modulation, aromatase inhibition, and selective estrogen-receptor degradation. Treatments that exploit these mechanisms have improved survival and quality of life for women with MBC. However, in many cases, resistance to ET limits their effectiveness. Elucidation of the complex cellular signal cascades involved in the development of acquired resistance to ET and the interrelationship of growth factor signaling and estrogen responsiveness have characterized components of these pathways as attractive targets for drug development. Based on these insights and with the aim of overcoming hormone resistance, targeted therapies are emerging as useful treatments for MBC. This article reviews current endocrine treatments of MBC as well as recent and ongoing study of combination treatments and targeted therapies that interfere with cellular proliferation pathways as means of overcoming resistance. The Oncologist 2017;22:507-517 IMPLICATIONS FOR PRACTICE: This review provides medical oncologists and other oncology health care providers with a current understanding of the rationale for endocrine therapy in estrogen receptor-positive metastatic breast cancer and the efficacy and safety profile of available treatment options. Additionally, current concepts regarding the development of treatment resistance and the treatment strategies for overcoming resistance are discussed. Enhancing the current information and the understanding of these topics will assist clinicians in evaluating optimal treatment options for their patients.

Project description:AimsCurrently, there are many approaches available for neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer that improve therapeutic efficacy but are also controversial. We conducted a two-step Bayesian network meta-analysis (NMA) to compare odds ratios (ORs) for pathologic complete response (PCR) and safety endpoints.MethodsThe Cochrane Central Register of Controlled Trials, PubMed, Embase, and online abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched comprehensively and systematically. Phase II/III randomised clinical trials for targeted therapy in at least one arm were included.ResultsA total of 9779 published manuscripts were identified, and 36 studies including 10,379 patients were finally included in our analysis. The NMA of PCR showed that dual-target therapy is better than single-target therapy and combination chemotherapy is better than monochemotherapy. However, anthracycline did not bring extra benefits, whether combined with dual-target therapy or single-target therapy. On the other hand, the addition of endocrine therapy in the HER2-positive, hormone receptor (HR)-positive subgroup might have additional beneficial effects but without significant statistical difference. By performing a conjoint analysis of the PCR rate and safety endpoints, we found that 'trastuzumab plus pertuzumab' and 'T-DM1 containing regimens' were well balanced in terms of efficacy and toxicity in all target regimens.ConclusionIn summary, trastuzumab plus pertuzumab-based dual-target therapy with combination chemotherapy regimens showed the highest efficacy of all optional regimens. They also achieved the best balance between efficacy and toxicity. As our study showed that anthracycline could be replaced by carboplatin, we strongly recommended TCbHP as the preferred choice for neoadjuvant treatment of HER2-positive breast cancer. We also look forward to the potential value of T-DM1 in improving outcomes, which needs further study in future trials.

Dataset Information

Network Meta-Analysis of the Effectiveness of Neoadjuvant Endocrine Therapy for Postmenopausal, HR-Positive Breast Cancer.

Publications

Network Meta-Analysis of the Effectiveness of Neoadjuvant Endocrine Therapy for Postmenopausal, HR-Positive Breast Cancer.

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