PMID- 30032196
OWN - NLM
STAT- MEDLINE
DCOM- 20200311
LR  - 20231006
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 111
IP  - 4
DP  - 2019 Apr 1
TI  - Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine 
      Therapy for HR+/HER2- Advanced Breast Cancer.
PG  - 419-430
LID - 10.1093/jnci/djy109 [doi]
AB  - BACKGROUND: Palbociclib administered with endocrine therapy was tolerable when 
      the overall incidence of toxicities was assessed separately for three PALOMA 
      studies. This study analyzed pooled, longer-term PALOMA safety data 
      longitudinally. METHODS: Data were pooled from three randomized phase II and III 
      studies (ClinicalTrials.gov: NCT00721409, NCT01740427, NCT01942135) of hormone 
      receptor-positive/human epidermal growth factor receptor 2‒negative advanced 
      breast cancer patients. Front-line patients were randomly assigned to receive 
      letrozole with/without palbociclib (PALOMA-1) or letrozole plus 
      palbociclib/placebo (PALOMA-2). In PALOMA-3, patients with prior endocrine 
      resistance received fulvestrant plus palbociclib/placebo. The cumulative event 
      rates of adverse events (AEs), reporting up to 50 months of treatment, were 
      assessed over time. RESULTS: Patients who received endocrine therapy (n = 1343) 
      were included in this pooled analysis (872 were also treated with palbociclib, 
      and 471 were not). The most common AEs with palbociclib plus endocrine therapy 
      were neutropenia and infections (any grade, 80.6% and 54.7%, respectively), which 
      were higher than in the endocrine monotherapy arm (any grade, 5.3% and 36.9%). 
      The most common hematologic AEs (>/=15.0% in the palbociclib arm) were more likely 
      to be reported in the initial months of the study, after which time the 
      cumulative event rate did not substantially increase. With palbociclib plus 
      endocrine therapy, any grade AEs leading to permanent discontinuation over three 
      years occurred in only 8.3% of patients. CONCLUSIONS: Based on these long-term 
      safety analyses, there is no evidence of specific cumulative or delayed 
      toxicities with palbociclib plus endocrine therapy, supporting the ongoing 
      investigation of palbociclib plus endocrine therapy in early breast cancer 
      (NCT02513394).
CI  - (c) The Author(s) 2018. Published by Oxford University Press.
FAU - Dieras, Veronique
AU  - Dieras V
AD  - Institut Curie, Paris, France (VD).
FAU - Rugo, Hope S
AU  - Rugo HS
AD  - University of California San Francisco Helen Diller Family Comprehensive Cancer 
      Center, San Francisco, CA (HSR).
FAU - Schnell, Patrick
AU  - Schnell P
AD  - Pfizer Inc, Collegeville, PA (PS, CHB).
FAU - Gelmon, Karen
AU  - Gelmon K
AD  - British Columbia Cancer Agency, Vancouver, BC, Canada (KG).
FAU - Cristofanilli, Massimo
AU  - Cristofanilli M
AD  - Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 
      Chicago, IL (MC).
FAU - Loi, Sherene
AU  - Loi S
AD  - Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia 
      (SL).
FAU - Colleoni, Marco
AU  - Colleoni M
AD  - Istituto Europeo di Oncologia, Milan, Italy (MC).
FAU - Lu, Dongrui R
AU  - Lu DR
AD  - Pfizer Inc, La Jolla, CA (DRL).
FAU - Mori, Ave
AU  - Mori A
AD  - Pfizer Inc, Milano, Italy (AM).
FAU - Gauthier, Eric
AU  - Gauthier E
AD  - Pfizer Inc, San Francisco, CA (EG).
FAU - Huang Bartlett, Cynthia
AU  - Huang Bartlett C
AD  - Pfizer Inc, Collegeville, PA (PS, CHB).
FAU - Slamon, Dennis J
AU  - Slamon DJ
AD  - David Geffen School of Medicine, Los Angeles, CA (DJS, RSF).
FAU - Turner, Nicholas C
AU  - Turner NC
AD  - Institute of Cancer Research and Royal Marsden Hospital, London, UK (NCT).
FAU - Finn, Richard S
AU  - Finn RS
AD  - David Geffen School of Medicine, Los Angeles, CA (DJS, RSF).
LA  - eng
SI  - ClinicalTrials.gov/NCT00721409
SI  - ClinicalTrials.gov/NCT01740427
SI  - ClinicalTrials.gov/NCT01942135
SI  - ClinicalTrials.gov/NCT02513394
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Estrogen)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - G9ZF61LE7G (palbociclib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/metabolism/pathology
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Fulvestrant/administration & dosage
MH  - Humans
MH  - Letrozole/administration & dosage
MH  - Middle Aged
MH  - Piperazines/administration & dosage
MH  - Prognosis
MH  - Pyridines/administration & dosage
MH  - Receptor, ErbB-2/*metabolism
MH  - Receptors, Estrogen/*metabolism
PMC - PMC6449170
EDAT- 2018/07/23 06:00
MHDA- 2020/03/12 06:00
PMCR- 2018/07/18
CRDT- 2018/07/23 06:00
PHST- 2017/08/23 00:00 [received]
PHST- 2018/04/10 00:00 [revised]
PHST- 2018/05/22 00:00 [accepted]
PHST- 2018/07/23 06:00 [pubmed]
PHST- 2020/03/12 06:00 [medline]
PHST- 2018/07/23 06:00 [entrez]
PHST- 2018/07/18 00:00 [pmc-release]
AID - 5055701 [pii]
AID - djy109 [pii]
AID - 10.1093/jnci/djy109 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2019 Apr 1;111(4):419-430. doi: 10.1093/jnci/djy109.