PMID- 34808438
OWN - NLM
STAT- MEDLINE
DCOM- 20211227
LR  - 20211227
IS  - 1532-3080 (Electronic)
IS  - 0960-9776 (Print)
IS  - 0960-9776 (Linking)
VI  - 60
DP  - 2021 Dec
TI  - Palbociclib dose reductions and the effect on clinical outcomes in patients with 
      advanced breast cancer.
PG  - 263-271
LID - S0960-9776(21)00995-4 [pii]
LID - 10.1016/j.breast.2021.11.013 [doi]
AB  - BACKGROUND: This study aimed to provide insights into the real-world use of 
      palbociclib, dose reductions, and drug effectiveness in (older) patients with 
      advanced breast cancer (BC). PATIENTS AND METHODS: Patients with advanced BC 
      treated with palbociclib from 2017 to 2020 were included. The Kaplan-Meier method 
      was used to calculate time to next treatment (TTNT) and overall survival (OS) for 
      patients with or without dose reductions. These clinical outcomes were also 
      compared in subgroup analyses for older patients (>/=70 years) and younger patients 
      (<70 years) and for patients discontinuing palbociclib early (<4 
      administrations). RESULTS: A total of 598 patients with advanced BC were 
      included, with a median age of 64 years. Palbociclib dose reductions occurred in 
      33% of all patients. Early discontinuation of palbociclib without dose reductions 
      occurred in 23% of the patients. Patients who required a palbociclib dose 
      reduction were older (median age 67 years vs. 63 years). Patients with dose 
      reductions had a significantly higher TTNT of 16.9 vs. 11.4 months (p < 0.001) 
      and median OS of 29.7 vs. 21.9 months (p = 0.003) compared to patients without 
      dose reductions. The TTNT in older patients was significantly longer (16.9 vs. 
      11.6 months, p = 0.013) than younger patients, but OS was similar (20.7 vs. 26.7 
      months, p = 0.051). CONCLUSION: Palbociclib dose reductions occurred in 
      real-world practice similarly to the PALOMA-3 trial. Patients with dose 
      reductions had no poorer outcomes compared to patients not requiring a dose 
      reduction. Older patients treated with palbociclib had more frequent dose 
      reductions, but this did not appear to affect OS.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Ismail, R K
AU  - Ismail RK
AD  - Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden, 2333AA, the 
      Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht 
      Institute for Pharmaceutical Sciences, Utrecht, the Netherlands. Electronic 
      address: r.ismail@dica.nl.
FAU - van Breeschoten, J
AU  - van Breeschoten J
AD  - Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden, 2333AA, the 
      Netherlands; Department of Medical Oncology, Amsterdam UMC, VU University Medical 
      Center, Cancer Center Amsterdam, De Boelelaan, 1118, Amsterdam, 1081HZ, the 
      Netherlands.
FAU - Wouters, M W J M
AU  - Wouters MWJM
AD  - Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden, 2333AA, the 
      Netherlands; Department of Surgical Oncology, Netherlands Cancer Institute, 
      Plesmanlaan 121, Amsterdam, 1066CX, the Netherlands; Department of Biomedical 
      Data Sciences, Leiden University Medical Centre, Albinusdreef 2, Leiden, 2333ZA, 
      the Netherlands.
FAU - van Dartel, M
AU  - van Dartel M
AD  - Medicines Evaluation Board, Graadt van Roggenweg 500, Utrecht, 3531AH, the 
      Netherlands.
FAU - van der Flier, S
AU  - van der Flier S
AD  - Cooperatie VGZ U.A, Nieuwe Stationsstraat 12, Arnhem, 6811KS, the Netherlands.
FAU - Reyners, A K L
AU  - Reyners AKL
AD  - Department of Medical Oncology, University Medical Center Groningen, University 
      of Groningen, Hanzeplein 1, Groningen, 9713 GZ, the Netherlands.
FAU - de Graeff, P
AU  - de Graeff P
AD  - University of Groningen, University Medical Center Groningen, University Center 
      for Geriatric Medicine, Hanzeplein 1, Groningen, 9700 RB, the Netherlands.
FAU - Pasmooij, A M G
AU  - Pasmooij AMG
AD  - Medicines Evaluation Board, Graadt van Roggenweg 500, Utrecht, 3531AH, the 
      Netherlands.
FAU - de Boer, A
AU  - de Boer A
AD  - Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for 
      Pharmaceutical Sciences, Utrecht, the Netherlands; Medicines Evaluation Board, 
      Graadt van Roggenweg 500, Utrecht, 3531AH, the Netherlands.
FAU - Broekman, K E
AU  - Broekman KE
AD  - Medicines Evaluation Board, Graadt van Roggenweg 500, Utrecht, 3531AH, the 
      Netherlands; Department of Medical Oncology, University Medical Center Groningen, 
      University of Groningen, Hanzeplein 1, Groningen, 9713 GZ, the Netherlands.
FAU - Hilarius, D L
AU  - Hilarius DL
AD  - Department of Pharmacy, Rode Kruis Ziekenhuis, Vondellaan 13, Beverwijk, 1942LE, 
      the Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20211117
PL  - Netherlands
TA  - Breast
JT  - Breast (Edinburgh, Scotland)
JID - 9213011
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - G9ZF61LE7G (palbociclib)
SB  - IM
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - *Breast Neoplasms/drug therapy
MH  - Drug Tapering
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Piperazines
MH  - Pyridines
MH  - Receptor, ErbB-2
PMC - PMC8609048
OTO - NOTNLM
OT  - Breast cancer
OT  - Clinical outcomes
OT  - Dose reductions
OT  - Older patients
OT  - Palbociclib
COIS- Declaration of competing interest The authors declare that they have no competing 
      interests.
EDAT- 2021/11/23 06:00
MHDA- 2021/12/28 06:00
PMCR- 2021/11/17
CRDT- 2021/11/22 20:19
PHST- 2021/11/01 00:00 [received]
PHST- 2021/11/16 00:00 [revised]
PHST- 2021/11/17 00:00 [accepted]
PHST- 2021/11/23 06:00 [pubmed]
PHST- 2021/12/28 06:00 [medline]
PHST- 2021/11/22 20:19 [entrez]
PHST- 2021/11/17 00:00 [pmc-release]
AID - S0960-9776(21)00995-4 [pii]
AID - 10.1016/j.breast.2021.11.013 [doi]
PST - ppublish
SO  - Breast. 2021 Dec;60:263-271. doi: 10.1016/j.breast.2021.11.013. Epub 2021 Nov 17.