Comment on Wang et al.: The efficacy of bevacizumab plus paclitaxel as first-line treatment for HER2-negative metastatic breast cancer: a meta-analysis of randomized controlled trials

Background: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (−) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach. Methods: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed. Results: First-line treatment options in HR+/HER2− MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53–0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53–0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47–0.86 for abemaciclib + AI) and patient’s characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors. Conclusions: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics.

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Anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11591 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11591-e11591

Author(s):

Pui San Tan ◽

Benjamin Haaland ◽

Alberto J. Montero ◽

Gilberto Lopes

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Combination Therapy ◽

Meta Analysis ◽

Metastatic Breast ◽

Line Treatment ◽

First Line ◽

Hormonal Receptor ◽

First Line Treatment

e11591 Background: Emerging resistance to single agent aromatase inhibitors (AI) or fulvestrant as first line treatment for postmenopausal women with advanced hormonal receptor positive breast cancer calls for alternative therapeutic options. This meta-analysis studies the effectiveness of combination therapy with fulvestrant and an AI, as compared to an AI alone in first line treatment of postmenopausal patients with hormonal receptor positive relapsed or metastatic breast cancer. Methods: Literature search was performed using PubMed, Google Scholar, Embase, ASCO and ESMO to search for studies published during the last 10 years using relevant keywords. Two prospective randomized clinical trials were found to fulfill the search criteria for combination of fulvestrant + AI vs. AI alone (both studied anastrozole in combination with fulvestrant). Meta-estimates were calculated by combining study estimates using the DerSimonian and Laird random effects model. The linear mixed-effects model was used to generate 95% prediction intervals for study-specific hazard and odds ratios. Results: Pooled hazard ratio for progression free survival was 0.88 (95% CI 0.72-1.09, 95% prediction interval [PI] 0.65-1.21). Pooled HR for overall survival was 0.88 (95% CI 0.72-1.08, 95% PI 0.68-1.14). Pooled odds ratio for response rate was 1.13 (95% CI 0.79-1.63, 95% PI 0.78-1.65). Conclusions: Pooled results showed a small, non-statistically significant, improvement in progression-free and overall survival. These results do not support the use of combination therapy with fulvestrant and anastrozole in the first line treatment of postmenopausal patients with hormonal receptor positive relapsed or metastatic breast cancer.

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