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

Mario Giuliano, Francesco Schettini, Carla Rognoni, Manuela Milani, Guy Jerusalem, Thomas Bachelot, Michelino De Laurentiis, Guglielmo Thomas, Pietro De Placido, Grazia Arpino, Sabino De Placido, Massimo Cristofanilli, Antonio Giordano, Fabio Puglisi, Barbara Pistilli, Aleix Prat, Lucia Del Mastro, Sergio Venturini, Daniele Generali

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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 first-line 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 survival. Moreover, no chemotherapy regimen with or without targeted therapy is significantly better than CDK4/6 inhibitors plus hormone therapies in terms of progression-free survival. Our data support treatment guideline recommendations involving the new combinations of hormone therapies plus targeted therapies as first-line or second-line treatments, or in both settings, in women with hormone-receptor-positive, HER2-negative metastatic breast cancer. Funding: None.

Original languageEnglish
Pages (from-to)1360-1369
Number of pages10
JournalThe Lancet Oncology
Volume20
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

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letrozole
Hormones
Breast Neoplasms
Drug Therapy
Therapeutics
Disease-Free Survival
Network Meta-Analysis
exemestane
Randomized Controlled Trials
Odds Ratio
Guidelines
Anthracyclines
Paclitaxel
PubMed
Language
palbociclib
Clinical Trials
Databases

ASJC Scopus subject areas

  • Oncology

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Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer : a systematic review and network meta-analysis. / Giuliano, Mario; Schettini, Francesco; Rognoni, Carla; Milani, Manuela; Jerusalem, Guy; Bachelot, Thomas; De Laurentiis, Michelino; Thomas, Guglielmo; De Placido, Pietro; Arpino, Grazia; De Placido, Sabino; Cristofanilli, Massimo; Giordano, Antonio; Puglisi, Fabio; Pistilli, Barbara; Prat, Aleix; Del Mastro, Lucia; Venturini, Sergio; Generali, Daniele.

In: The Lancet Oncology, Vol. 20, No. 10, 01.10.2019, p. 1360-1369.

Research output: Contribution to journalArticle

Giuliano, M, Schettini, F, Rognoni, C, Milani, M, Jerusalem, G, Bachelot, T, De Laurentiis, M, Thomas, G, De Placido, P, Arpino, G, De Placido, S, Cristofanilli, M, Giordano, A, Puglisi, F, Pistilli, B, Prat, A, Del Mastro, L, Venturini, S & Generali, D 2019, 'Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis', The Lancet Oncology, vol. 20, no. 10, pp. 1360-1369. https://doi.org/10.1016/S1470-2045(19)30420-6
Giuliano, Mario ; Schettini, Francesco ; Rognoni, Carla ; Milani, Manuela ; Jerusalem, Guy ; Bachelot, Thomas ; De Laurentiis, Michelino ; Thomas, Guglielmo ; De Placido, Pietro ; Arpino, Grazia ; De Placido, Sabino ; Cristofanilli, Massimo ; Giordano, Antonio ; Puglisi, Fabio ; Pistilli, Barbara ; Prat, Aleix ; Del Mastro, Lucia ; Venturini, Sergio ; Generali, Daniele. / Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer : a systematic review and network meta-analysis. In: The Lancet Oncology. 2019 ; Vol. 20, No. 10. pp. 1360-1369.
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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 first-line 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 survival. Moreover, no chemotherapy regimen with or without targeted therapy is significantly better than CDK4/6 inhibitors plus hormone therapies in terms of progression-free survival. Our data support treatment guideline recommendations involving the new combinations of hormone therapies plus targeted therapies as first-line or second-line treatments, or in both settings, in women with hormone-receptor-positive, HER2-negative metastatic breast cancer. Funding: None.",
author = "Mario Giuliano and Francesco Schettini and Carla Rognoni and Manuela Milani and Guy Jerusalem and Thomas Bachelot and {De Laurentiis}, Michelino and Guglielmo Thomas and {De Placido}, Pietro and Grazia Arpino and {De Placido}, Sabino and Massimo Cristofanilli and Antonio Giordano and Fabio Puglisi and Barbara Pistilli and Aleix Prat and {Del Mastro}, Lucia and Sergio Venturini and Daniele Generali",
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TY - JOUR

T1 - Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer

T2 - a systematic review and network meta-analysis

AU - Giuliano, Mario

AU - Schettini, Francesco

AU - Rognoni, Carla

AU - Milani, Manuela

AU - Jerusalem, Guy

AU - Bachelot, Thomas

AU - De Laurentiis, Michelino

AU - Thomas, Guglielmo

AU - De Placido, Pietro

AU - Arpino, Grazia

AU - De Placido, Sabino

AU - Cristofanilli, Massimo

AU - Giordano, Antonio

AU - Puglisi, Fabio

AU - Pistilli, Barbara

AU - Prat, Aleix

AU - Del Mastro, Lucia

AU - Venturini, Sergio

AU - Generali, Daniele

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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 first-line 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 survival. Moreover, no chemotherapy regimen with or without targeted therapy is significantly better than CDK4/6 inhibitors plus hormone therapies in terms of progression-free survival. Our data support treatment guideline recommendations involving the new combinations of hormone therapies plus targeted therapies as first-line or second-line treatments, or in both settings, in women with hormone-receptor-positive, HER2-negative metastatic breast cancer. Funding: None.

AB - 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 first-line 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 survival. Moreover, no chemotherapy regimen with or without targeted therapy is significantly better than CDK4/6 inhibitors plus hormone therapies in terms of progression-free survival. Our data support treatment guideline recommendations involving the new combinations of hormone therapies plus targeted therapies as first-line or second-line treatments, or in both settings, in women with hormone-receptor-positive, HER2-negative metastatic breast cancer. Funding: None.

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