PMID- 28618307
OWN - NLM
STAT- MEDLINE
DCOM- 20180528
LR  - 20220317
IS  - 1532-3080 (Electronic)
IS  - 0960-9776 (Linking)
VI  - 35
DP  - 2017 Oct
TI  - Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: Palbociclib 
      and ribociclib.
PG  - 1-7
LID - S0960-9776(17)30461-7 [pii]
LID - 10.1016/j.breast.2017.05.016 [doi]
AB  - PURPOSE: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib 
      and ribociclib are associated with distinct adverse effects (AEs) compared to 
      other targeted therapies. This meta-analysis of clinical trials summarizes these 
      agents' toxicity profile. METHODS: A librarian-guided literature search was 
      conducted in March of 2017. The trials needed to have at least one of the study 
      arms consisting of palbociclib or ribociclib monotherapy at currently FDA 
      approved dose regimens. Heterogeneity across studies was analyzed using I(2) 
      statistics. Data were analyzed using random effects meta-analysis for absolute 
      risks. RESULTS: Seven randomized trials and 1,332 patients were included in our 
      meta-analysis. There was evidence of significant heterogeneity between studies 
      for serious AEs but not for death. The pooled absolute risk (AR) for 
      all-causality serious AEs and treatment-related death were 16% and 0%, 
      respectively. Patients treated with CDK 4/6 inhibitors had an AR of grade 3/4 
      neutropenia of 61%; neutropenic fever and infections were rare (1% and 3%, 
      respectively). Grade 3/4 nausea, vomiting, and rash were rare. There was no 
      significant correlation between age of patients at study entry and the risk of 
      grade 3/4 neutropenia. CONCLUSION: Treatment with CDK 4/6 inhibitors is well 
      tolerated and associated with a low risk of treatment-related deaths. There is an 
      increased AR of grade 3/4 neutropenia but a low AR of associated infections.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Costa, R
AU  - Costa R
AD  - Division of Hematology Oncology, Northwestern University Feinberg School of 
      Medicine, Chicago, IL, USA. Electronic address: ricardo.costa@northwestern.edu.
FAU - Costa, R B
AU  - Costa RB
AD  - Division of Hematology Oncology, Northwestern University Feinberg School of 
      Medicine, Chicago, IL, USA.
FAU - Talamantes, Sarah M
AU  - Talamantes SM
AD  - Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
FAU - Helenowski, Irene
AU  - Helenowski I
AD  - Northwestern University Department of Preventive Medicine, Chicago, IL, USA.
FAU - Peterson, Jonna
AU  - Peterson J
AD  - Galter Health Sciences Library, Northwestern University, Chicago, IL, USA.
FAU - Kaplan, Jason
AU  - Kaplan J
AD  - Division of Hematology Oncology, Northwestern University Feinberg School of 
      Medicine, Chicago, IL, USA.
FAU - Carneiro, B A
AU  - Carneiro BA
AD  - Division of Hematology Oncology, Northwestern University Feinberg School of 
      Medicine, Chicago, IL, USA.
FAU - Giles, Francis J
AU  - Giles FJ
AD  - Division of Hematology Oncology, Northwestern University Feinberg School of 
      Medicine, Chicago, IL, USA.
FAU - Gradishar, W J
AU  - Gradishar WJ
AD  - Division of Hematology Oncology, Northwestern University Feinberg School of 
      Medicine, Chicago, IL, USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
DEP - 20170612
PL  - Netherlands
TA  - Breast
JT  - Breast (Edinburgh, Scotland)
JID - 9213011
RN  - 0 (Aminopyridines)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Pyridines)
RN  - G9ZF61LE7G (palbociclib)
RN  - TK8ERE8P56 (ribociclib)
SB  - IM
MH  - Aminopyridines/administration & dosage/*adverse effects
MH  - Antineoplastic Agents/administration & dosage/*adverse effects
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Molecular Targeted Therapy
MH  - Neutropenia/chemically induced
MH  - Piperazines/administration & dosage/*adverse effects
MH  - Purines/administration & dosage/*adverse effects
MH  - Pyridines/administration & dosage/*adverse effects
OTO - NOTNLM
OT  - Infection
OT  - Neutropenia
OT  - Palbociclib
OT  - Ribociclib
EDAT- 2017/06/16 06:00
MHDA- 2018/05/29 06:00
CRDT- 2017/06/16 06:00
PHST- 2017/05/11 00:00 [received]
PHST- 2017/05/30 00:00 [revised]
PHST- 2017/05/31 00:00 [accepted]
PHST- 2017/06/16 06:00 [pubmed]
PHST- 2018/05/29 06:00 [medline]
PHST- 2017/06/16 06:00 [entrez]
AID - S0960-9776(17)30461-7 [pii]
AID - 10.1016/j.breast.2017.05.016 [doi]
PST - ppublish
SO  - Breast. 2017 Oct;35:1-7. doi: 10.1016/j.breast.2017.05.016. Epub 2017 Jun 12.