PMID- 30375908
OWN - NLM
STAT- MEDLINE
DCOM- 20190604
LR  - 20191210
IS  - 1651-226X (Electronic)
IS  - 0284-186X (Linking)
VI  - 58
IP  - 2
DP  - 2019 Feb
TI  - Treatment of advanced HR+/HER2- breast cancer with new targeted agents in 
      combination with endocrine therapy: a review of efficacy and tolerability based 
      on available randomized trials on everolimus, ribociclib, palbociclib and 
      abemaciclib.
PG  - 147-153
LID - 10.1080/0284186X.2018.1532603 [doi]
AB  - INTRODUCTION: Recently, new targeted agents have been developed, which can 
      prolong the effect of endocrine treatment (ET) by targeting resistance pathways 
      in HR+/HER2- advanced breast cancer. This review examines available studies of 
      everolimus, an mTOR inhibitor, and the CDK 4/6 inhibitors ribociclib, palbociclib 
      and abemaciclib in terms of efficacy, tolerability and safety. MATERIAL AND 
      METHODS: A systematic literature search was performed in Pubmed. Evaluation of 
      the quality of the identified studies was based on selected elements from the 
      GRADE guidelines. RESULTS: The literature search yielded eight randomized trials 
      that all presented a significant increase in the progression free survival 
      (PFS)/time to progression (TTP) for the targeted agents plus ET vs ET only. The 
      improvement was evident as first-line therapy with an increase in PFS of 10-11 
      months when adding a CDK4/6 inhibitor to ET, as well as in patients previously 
      treated for metastatic disease, with an increase of 5-6 months. The common 
      adverse events (AEs) of the CDK 4/6 inhibitors were due to myelosuppression. In 
      addition, abemaciclib was associated with liver toxicity and diarrhea, and 
      ribociclib with liver toxicity and QTcF prolongation. The most common grade 3/4 
      AE of everolimus was stomatitis. The majority (five) of the trials had no serious 
      limitations, and thus the quality of evidence was high. DISCUSSION: The new 
      targeted agents are all associated with an improvement of the PFS with an 
      acceptable tolerability, and they should be offered to women with advanced 
      HR+/HER2- breast cancer both as first-line therapy as well as among patients 
      previously treated in metastatic regimens. However, further data regarding the 
      impact on overall survival are required to evaluate the full benefit for 
      patients. Price and differences in AEs could become substantial arguments for the 
      choice of therapy for the individual patient.
FAU - Bottcher, Tea M
AU  - Bottcher TM
AD  - a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
FAU - Cold, Soren
AU  - Cold S
AD  - b Department of Oncology , Odense University Hospital , Odense , Denmark.
FAU - Jensen, Anders B
AU  - Jensen AB
AD  - a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
LA  - eng
PT  - Journal Article
PT  - Systematic Review
DEP - 20181030
PL  - Sweden
TA  - Acta Oncol
JT  - Acta oncologica (Stockholm, Sweden)
JID - 8709065
RN  - 0 (Aminopyridines)
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Benzimidazoles)
RN  - 0 (Drugs, Investigational)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 60UAB198HK (abemaciclib)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - G9ZF61LE7G (palbociclib)
RN  - TK8ERE8P56 (ribociclib)
SB  - IM
MH  - Aminopyridines/administration & dosage/adverse effects
MH  - Antineoplastic Agents, Hormonal/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Benzimidazoles/administration & dosage/adverse effects
MH  - Breast Neoplasms/*drug therapy/epidemiology/genetics/pathology
MH  - Disease Progression
MH  - Drugs, Investigational/therapeutic use
MH  - Everolimus/administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Molecular Targeted Therapy/methods/trends
MH  - Piperazines/administration & dosage/adverse effects
MH  - Purines/administration & dosage/adverse effects
MH  - Pyridines/administration & dosage/adverse effects
MH  - Randomized Controlled Trials as Topic/statistics & numerical data
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Treatment Outcome
EDAT- 2018/10/31 06:00
MHDA- 2019/06/05 06:00
CRDT- 2018/10/31 06:00
PHST- 2018/10/31 06:00 [pubmed]
PHST- 2019/06/05 06:00 [medline]
PHST- 2018/10/31 06:00 [entrez]
AID - 10.1080/0284186X.2018.1532603 [doi]
PST - ppublish
SO  - Acta Oncol. 2019 Feb;58(2):147-153. doi: 10.1080/0284186X.2018.1532603. Epub 2018 
      Oct 30.