PMID- 32468645
OWN - NLM
STAT- MEDLINE
DCOM- 20210730
LR  - 20210730
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 60
IP  - 10
DP  - 2020 Oct
TI  - Exposure-Safety Analyses of Talazoparib in Patients With Advanced Breast Cancer 
      and Germline BRCA1/2 Mutations in the EMBRACA and ABRAZO Trials.
PG  - 1334-1343
LID - 10.1002/jcph.1626 [doi]
AB  - Poly(ADP-ribose) polymerase inhibitors, such as talazoparib, may affect 
      hematopoiesis. This analysis characterized the relationship between talazoparib 
      exposure and the most common grade >/= 3 hematopoietic adverse events (AEs) leading 
      to dose modification in the phase 2 (ABRAZO) and phase 3 (EMBRACA) trials. The 
      relationship between time-varying average talazoparib concentration (C(avg,t) ), 
      along with other baseline variables, and grade >/= 3 anemia, thrombocytopenia, and 
      neutropenia were evaluated both by graphical examination and using univariate and 
      multivariate Cox proportional hazard models. The results indicated that higher 
      C(avg,t) was associated with a higher risk of anemia and thrombocytopenia. A 
      trend toward an association between higher C(avg,t) and neutropenia was observed, 
      although not statistically significant. Higher risk of all tested safety end 
      points was associated with lower baseline hemoglobin. Higher risk of neutropenia 
      was associated with lower baseline absolute neutrophil count and lower body 
      weight. These findings support the proposed management of AEs through talazoparib 
      dosing modification.
CI  - (c) 2020, The American College of Clinical Pharmacology.
FAU - Elmeliegy, Mohamed
AU  - Elmeliegy M
AUID- ORCID: 0000-0002-9825-5890
AD  - Pfizer Inc., La Jolla, California, USA.
FAU - Yu, Yanke
AU  - Yu Y
AD  - Pfizer Inc., La Jolla, California, USA.
FAU - Litton, Jennifer K
AU  - Litton JK
AD  - The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Czibere, Akos
AU  - Czibere A
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Wilson, Gary G
AU  - Wilson GG
AD  - Pfizer Inc., New York, New York, USA.
FAU - Tudor, Iulia Cristina
AU  - Tudor IC
AD  - Pfizer Inc., San Francisco, California, USA.
FAU - Zheng, Jenny
AU  - Zheng J
AD  - Pfizer Inc., Collegeville, Pennsylvania, USA.
FAU - Wang, Diane D
AU  - Wang DD
AD  - Pfizer Inc., La Jolla, California, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200528
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phthalazines)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 9QHX048FRV (talazoparib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia/chemically induced
MH  - Antineoplastic Agents/administration & dosage/*adverse 
      effects/blood/pharmacokinetics
MH  - Breast Neoplasms/*drug therapy/*genetics
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Dosage Calculations
MH  - Female
MH  - Genes, BRCA1
MH  - Genes, BRCA2
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Middle Aged
MH  - Mutation
MH  - Neutropenia/chemically induced
MH  - Phthalazines/administration & dosage/*adverse effects/blood/pharmacokinetics
MH  - Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage/*adverse 
      effects/blood/pharmacokinetics
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Thrombocytopenia/chemically induced
OTO - NOTNLM
OT  - BRCA mutation
OT  - PARP inhibitor
OT  - advanced breast cancer
OT  - breast cancer
OT  - exposure-safety
OT  - talazoparib
EDAT- 2020/05/30 06:00
MHDA- 2021/07/31 06:00
CRDT- 2020/05/30 06:00
PHST- 2019/11/29 00:00 [received]
PHST- 2020/03/25 00:00 [accepted]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/07/31 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
AID - 10.1002/jcph.1626 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2020 Oct;60(10):1334-1343. doi: 10.1002/jcph.1626. Epub 2020 
      May 28.