Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis

Abstract

Background Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatments, or both, based on chemotherapy and on hormone therapy have been scarcely investigated in head-to-head randomised controlled trials, we aimed to compare these two different approaches. Methods We did a systematic review and network meta-analysis with a systematic literature search on PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, and online archives of the most relevant international oncology conferences. We included all phase 2 and 3 randomised controlled trials investigating chemotherapy with or without targeted therapies and hormone therapies with or without targeted therapies as firstline or second-line treatments, or both, in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, published between Jan 1, 2000, and Dec 31, 2017. Additional recently published randomised controlled trials relevant to the topic were also subsequently added. No language restrictions were adopted for our search. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for progression-free survival (the primary outcome), and to compare odds ratios (ORs) for the proportion of patients achieving an overall response (the secondary outcome). All treatments were compared to anastrozole and to palbociclib plus letrozole. This study is registered in the Open Science Framework online public database, registration DOI 10.17605/OSF.IO/496VR. Findings We identified 2689 published results and 140 studies (comprising 50 029 patients) were included in the analysis. Palbociclib plus letrozole (HR 0•42; 95% credible interval [CrI] 0•25-0•70), ribociclib plus letrozole (0•43; 0•24-0•77), abemaciclib plus anastrozole or letrozole (0•42; 0•23-0•76), palbociclib plus fulvestrant (0•37; 0•23-0•59), ribociclib plus fulvestrant (0•48; 0•31-0•74), abemaciclib plus fulvestrant (0•44; 0•28-0•70), everolimus plus exemestane (0•42; 0•28-0•67), and, in patients with a PIK3CA mutation, alpelisib plus fulvestrant (0•39; 0•22-0•66), and several chemotherapy-based regimens, including anthracycline and taxane-containing regimens, were associated with better progression-free survival than was anastrozole alone. No chemotherapy or hormone therapy regimen was significantly better than palbociclib plus letrozole for progression-free survival. Paclitaxel plus bevacizumab was the only clinically relevant regimen that was significantly better than palbociclib plus letrozole in terms of the proportion of patients achieving an overall response (OR 8•95; 95% CrI 1•03-76•92). Interpretation In the first-line or second-line setting, CDK4/6 inhibitors plus hormone therapies are better than standard hormone therapies in terms of progression-free surv...

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis

“…Another recent and very large network meta-analysis has evaluated all chemotherapy and ET-based treatments in postmenopausal women with HR+/HER2− metastatic breast cancer. 80 Similarly to our results, it has showed that CDK4/6i plus ET are better than standard ET; in addition, it has demonstrated that no chemotherapy regimen was significantly better than CDK4/6i plus ET in terms of PFS. However, this network meta-analysis did not include premenopausal women, did not provide OS data or analysed efficacy according to endocrine-sensitivity status or different patients' subgroups (visceral disease, bone-only, etc).…”

Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study

“…After that, newer effective treatment strategies based on CDK4/6 inhibitors combined with aromatase inhibitors or fulvestrant and the PI3K inhibitor alpelisib combined with fulvestrant for PIK3CA-mutant patients have also been added to the therapeutic armamentarium in the last few years [ 35 – 37 ]. A recent comprehensive network meta-analysis highlighted comparable therapeutic performances between such therapies and chemotherapy [ 38 ]. However, at present, the optimal treatment sequence is not known, as there is a lack of direct comparisons and no effective biomarkers of response for all these treatment strategies.…”

CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer

“…In women, breast cancer represents nearly one-third of newly diagnosed cancers and is the most common cancer in women from ages 20 to 59 (1). Currently, breast cancer treatments are based on the expression of biomarkers, such as progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (EGFR2, also known as HER2) (1,2). Good clinical outcomes have been observed after anti-hormonal therapies in tumors expressing ER, although these therapies lead to resistance, limiting the effectiveness of hormone-based therapy (3).…”