PMID- 30054831
OWN - NLM
STAT- MEDLINE
DCOM- 20190108
LR  - 20190418
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 172
IP  - 1
DP  - 2018 Nov
TI  - CDK4/6 inhibitors in advanced hormone receptor-positive/HER2-negative breast 
      cancer: a systematic review and meta-analysis of randomized trials.
PG  - 9-21
LID - 10.1007/s10549-018-4901-0 [doi]
AB  - PURPOSE: Combining CDK4/6 inhibitors and endocrine therapy (ET) improved outcomes 
      for the treatment of metastatic HR+/HER2- breast cancers. Here, we performed a 
      meta-analysis of randomized clinical trials (RCTs) to better define the benefit 
      and the risk of CDK4/6 inhibitors plus ET for endocrine-sensitive or 
      endocrine-resistant population in metastatic HR+/HER2- breast cancer. METHOD: A 
      systematic literature search of Pubmed, Embase, and the Cochrane Library was 
      carried out up to 30 June 2018. Hazard ratios (HRs) and 95% confidence intervals 
      (CIs) for progression-free survival (PFS), as well as odds ratios (ORs) for 
      objective response rates, >/= G3-G4 adverse events (AEs), and G3-G4 neutropenia 
      were calculated for each trial. A meta-analysis was carried out using the 
      random-effects model. RESULTS: Eight RCTs were eligible including 4578 breast 
      cancer patients. Adding CDK4/6 inhibitors to ET in endocrine-sensitive (HR 0.55, 
      95% CI 0.50-0.62) or endocrine-resistant setting (HR 0.51, 95% CI 0.43-0.61) 
      significantly improved the PFS of metastatic HR+/HER2- breast cancers regardless 
      of menopausal status and site of metastasis. Moreover, CDK4/6 inhibitors plus ET 
      meaningfully improved objective response rate in endocrine-sensitive (ORs 0.62, 
      95% CI 0.52-0.73) or endocrine-resistant setting (ORs 0.33, 95% CI 0.24-0.47). 
      The use of these drugs was characterized by a significant increase of G3-G4 AEs 
      (OR 10.88, 95% CI 6.53-18.14). CONCLUSION: Emerging data provide a new standard 
      treatment for advanced HR+/HER2- breast cancer, regardless of menopausal status, 
      prior hormonal/chemotherapy treatments delivered, sites of metastasis. However, 
      benefits should be balanced with longer treatment duration, toxicities, and 
      costs.
FAU - Messina, Carlo
AU  - Messina C
AUID- ORCID: 0000-0002-7934-1419
AD  - Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. 
      Benzi 10, 16132, Genoa, Italy. carlo.messi@hotmail.it.
AD  - Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, 
      Italy. carlo.messi@hotmail.it.
FAU - Cattrini, Carlo
AU  - Cattrini C
AD  - Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. 
      Benzi 10, 16132, Genoa, Italy.
AD  - Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, 
      Italy.
FAU - Buzzatti, Giulia
AU  - Buzzatti G
AD  - Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. 
      Benzi 10, 16132, Genoa, Italy.
AD  - Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, 
      Italy.
FAU - Cerbone, Luigi
AU  - Cerbone L
AD  - Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. 
      Benzi 10, 16132, Genoa, Italy.
AD  - Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, 
      Italy.
FAU - Zanardi, Elisa
AU  - Zanardi E
AD  - Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. 
      Benzi 10, 16132, Genoa, Italy.
AD  - Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, 
      Italy.
FAU - Messina, Marco
AU  - Messina M
AD  - Oncology Unit, Istituto Fondazione G. Giglio, Cefalu, Italy.
FAU - Boccardo, Francesco
AU  - Boccardo F
AD  - Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. 
      Benzi 10, 16132, Genoa, Italy.
AD  - Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, 
      Italy.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20180727
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (CDK6 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
SB  - IM
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - Cyclin-Dependent Kinase 4/*antagonists & inhibitors/genetics
MH  - Cyclin-Dependent Kinase 6/*antagonists & inhibitors/genetics
MH  - Female
MH  - Humans
MH  - Neoplasm Metastasis
MH  - Progression-Free Survival
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Receptor, ErbB-2/genetics
MH  - Receptors, Estrogen/genetics
MH  - Receptors, Progesterone/genetics
OTO - NOTNLM
OT  - Abemaciclib
OT  - Breast cancer
OT  - Hormonal therapy
OT  - Meta-analysis
OT  - Palbociclib
OT  - Ribociclib
EDAT- 2018/07/29 06:00
MHDA- 2019/01/09 06:00
CRDT- 2018/07/29 06:00
PHST- 2018/05/19 00:00 [received]
PHST- 2018/07/23 00:00 [accepted]
PHST- 2018/07/29 06:00 [pubmed]
PHST- 2019/01/09 06:00 [medline]
PHST- 2018/07/29 06:00 [entrez]
AID - 10.1007/s10549-018-4901-0 [pii]
AID - 10.1007/s10549-018-4901-0 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2018 Nov;172(1):9-21. doi: 10.1007/s10549-018-4901-0. 
      Epub 2018 Jul 27.