Systematic Review and Network Meta-analysis Comparing Palbociclib with Chemotherapy Agents for the Treatment of Postmenopausal Women with HR-positive and HER2-negative Advanced/metastatic Breast Cancer

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2017 Jul 29

PMID 28752187

Citations 13

Authors

Florence R Wilson

Abhishek Varu

Debanjali Mitra

Chris Cameron

Shrividya Iyer

Affiliations

Soon will be listed here.

Abstract

Purpose: To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line).

Methods: A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC. The main outcome of interest was progression-free survival (PFS)/time to progression (TTP). Bayesian network meta-analyses (NMAs) and pairwise meta-analyses were conducted. Heterogeneity and inconsistency were assessed.

Results: Sixty RCTs met eligibility criteria and were stratified by line of therapy. In the first line, palbociclib + letrozole showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11-0.72)] and mitoxantrone [HR 0.28 (0.13-0.61)], and trended toward improvements versus paclitaxel [HR 0.59 (0.19-1.96)], docetaxel [HR 0.51 (0.14-2.03)] and other monotherapy or combination agents (HRs ranging from 0.24 to 0.99). In the second line, palbociclib + fulvestrant showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13-0.65)], mitoxantrone [HR 0.26 (0.12-0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07-0.50)], and trended toward improvements versus paclitaxel [HR 0.48 (0.16-1.44)], docetaxel [HR 0.71 (0.24-2.13)] and other monotherapy or combination agents (HRs ranging from 0.23-0.89). NMA findings aligned with direct evidence and were robust to sensitivity analyses.

Conclusions: Palbociclib + letrozole and palbociclib + fulvestrant demonstrate trends in incremental efficacy compared with chemotherapy agents for the first- and second-line treatment of HR +/HER2- ABC/MBC.

Citing Articles

The Renaissance of CDK Inhibitors in Breast Cancer Therapy: An Update on Clinical Trials and Therapy Resistance.

Abdelmalak M, Singh R, Anwer M, Ivanchenko P, Randhawa A, Ahmed M Cancers (Basel). 2022; 14(21).

PMID: 36358806 PMC: 9655989. DOI: 10.3390/cancers14215388.

Cost Effectiveness of Ribociclib and Palbociclib in the Second-Line Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer in Post-Menopausal Indian Women.

Gupta N, Gupta D, Dixit J, Mehra N, Singh A, Krishnamurthy M Appl Health Econ Health Policy. 2022; 20(4):609-621.

PMID: 35534752 DOI: 10.1007/s40258-022-00731-2.

Network meta-analysis of eribulin versus other chemotherapies used as second- or later-line treatment in locally advanced or metastatic breast cancer.

Zhao Q, Hughes R, Neupane B, Mickle K, Su Y, Chabot I BMC Cancer. 2021; 21(1):758.

PMID: 34193107 PMC: 8244131. DOI: 10.1186/s12885-021-08446-8.

Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis.

Schettini F, Giuliano M, Giudici F, Conte B, De Placido P, Venturini S Cancers (Basel). 2021; 13(6).

PMID: 33810205 PMC: 8004645. DOI: 10.3390/cancers13061458.

Association of Cyclin-Dependent Kinases 4 and 6 Inhibitors With Survival in Patients With Hormone Receptor-Positive Metastatic Breast Cancer: A Systematic Review and Meta-analysis.

Li J, Huo X, Zhao F, Ren D, Ahmad R, Yuan X JAMA Netw Open. 2020; 3(10):e2020312.

PMID: 33048129 PMC: 8094425. DOI: 10.1001/jamanetworkopen.2020.20312.

References

Cardoso F, Costa A, Norton L, Senkus E, Aapro M, Andre F . ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)†. Ann Oncol. 2014; 25(10):1871-1888. PMC: 4176456. DOI: 10.1093/annonc/mdu385. View

Wolters R, Regierer A, Schwentner L, Geyer V, Possinger K, Kreienberg R . A comparison of international breast cancer guidelines - do the national guidelines differ in treatment recommendations?. Eur J Cancer. 2011; 48(1):1-11. DOI: 10.1016/j.ejca.2011.06.020. View

Salanti G, Ades A, Ioannidis J . Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2010; 64(2):163-71. DOI: 10.1016/j.jclinepi.2010.03.016. View

Cristofanilli M, Turner N, Bondarenko I, Ro J, Im S, Masuda N . Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre,.... Lancet Oncol. 2016; 17(4):425-439. DOI: 10.1016/S1470-2045(15)00613-0. View

Dias S, Welton N, Sutton A, Ades A . Evidence synthesis for decision making 1: introduction. Med Decis Making. 2013; 33(5):597-606. PMC: 3704205. DOI: 10.1177/0272989X13487604. View

Wang J, Xu B, Yuan P, Ma F, Li Q, Zhang P . Capecitabine combined with docetaxel versus vinorelbine followed by capecitabine maintenance medication for first-line treatment of patients with advanced breast cancer: Phase 3 randomized trial. Cancer. 2015; 121(19):3412-21. DOI: 10.1002/cncr.29492. View

Bachelot T, Bajard A, Ray-Coquard I, Provencal J, Coeffic D, Agostini C . Final results of ERASME-4: a randomized trial of first-line docetaxel plus either capecitabine or epirubicin for metastatic breast cancer. Oncology. 2011; 80(3-4):262-8. DOI: 10.1159/000329066. View

Chirila C, Mitra D, Colosia A, Ling C, Odom D, Iyer S . Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis. Curr Med Res Opin. 2017; 33(8):1457-1466. DOI: 10.1080/03007995.2017.1325730. View

Generali D, Venturini S, Rognoni C, Ciani O, Pusztai L, Loi S . A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer. Breast Cancer Res Treat. 2015; 152(1):95-117. DOI: 10.1007/s10549-015-3453-9. View

10.

Hutton B, Salanti G, Caldwell D, Chaimani A, Schmid C, Cameron C . The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015; 162(11):777-84. DOI: 10.7326/M14-2385. View

11.

Cameron C, Fireman B, Hutton B, Clifford T, Coyle D, Wells G . Network meta-analysis incorporating randomized controlled trials and non-randomized comparative cohort studies for assessing the safety and effectiveness of medical treatments: challenges and opportunities. Syst Rev. 2015; 4:147. PMC: 4634799. DOI: 10.1186/s13643-015-0133-0. View

12.

Joy A, Ghosh M, Fernandes R, Clemons M . Systemic treatment approaches in her2-negative advanced breast cancer-guidance on the guidelines. Curr Oncol. 2015; 22(Suppl 1):S29-42. PMC: 4381789. DOI: 10.3747/co.22.2360. View

13.

Cameron C, Coyle D, Richter T, Kelly S, Gauthier K, Steiner S . Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation. BMJ Open. 2014; 4(6):e004301. PMC: 4054633. DOI: 10.1136/bmjopen-2013-004301. View

14.

Rhodes K, Turner R, Higgins J . Predictive distributions were developed for the extent of heterogeneity in meta-analyses of continuous outcome data. J Clin Epidemiol. 2014; 68(1):52-60. PMC: 4270451. DOI: 10.1016/j.jclinepi.2014.08.012. View

15.

McIntosh B, Cameron C, Singh S, Yu C, Ahuja T, Welton N . Second-line therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a systematic review and mixed-treatment comparison meta-analysis. Open Med. 2011; 5(1):e35-48. PMC: 3205809. View

16.

Dias S, Sutton A, Ades A, Welton N . Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making. 2012; 33(5):607-17. PMC: 3704203. DOI: 10.1177/0272989X12458724. View

17.

Finn R, Martin M, Rugo H, Jones S, Im S, Gelmon K . Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016; 375(20):1925-1936. DOI: 10.1056/NEJMoa1607303. View

18.

Ackland S, Anton A, Breitbach G, Colajori E, Tursi J, Delfino C . Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study. J Clin Oncol. 2001; 19(4):943-53. DOI: 10.1200/JCO.2001.19.4.943. View

19.

Paridaens R, Biganzoli L, Bruning P, Klijn J, Gamucci T, Houston S . Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol. 2000; 18(4):724-33. DOI: 10.1200/JCO.2000.18.4.724. View

20.

Dias S, Welton N, Sutton A, Caldwell D, Lu G, Ades A . Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making. 2013; 33(5):641-56. PMC: 3704208. DOI: 10.1177/0272989X12455847. View