PMID- 30515674
OWN - NLM
STAT- MEDLINE
DCOM- 20190529
LR  - 20221207
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Print)
IS  - 1341-9625 (Linking)
VI  - 24
IP  - 3
DP  - 2019 Mar
TI  - Palbociclib in combination with letrozole in patients with estrogen 
      receptor-positive, human epidermal growth factor receptor 2-negative advanced 
      breast cancer: PALOMA-2 subgroup analysis of Japanese patients.
PG  - 274-287
LID - 10.1007/s10147-018-1353-9 [doi]
AB  - BACKGROUND: In PALOMA-2, palbociclib-letrozole significantly improved 
      progression-free survival (PFS) vs placebo-letrozole in women with estrogen 
      receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) 
      advanced breast cancer (ABC) in the first-line setting. We evaluated the 
      efficacy, safety, and pharmacokinetics of palbociclib in Japanese women in 
      PALOMA-2. METHODS: In this phase 3 study, 666 postmenopausal women with ER+/HER2- 
      ABC were randomized 2:1 to palbociclib (125 mg/day [3 weeks on/1 week off]) plus 
      letrozole (2.5 mg daily) or placebo plus letrozole. A prespecified, exploratory, 
      subgroup analysis of Japanese patients (n = 46) was conducted to compare results 
      with those of the overall population. RESULTS: At the February 26, 2016 cutoff, 
      median PFS among the 46 Japanese patients was 22.2 months (95%CI, 13.6‒not 
      estimable) with palbociclib-letrozole vs 13.8 months (5.6‒22.2) with 
      placebo-letrozole (hazard ratio, 0.59 [95%CI, 0.26-1.34]). The most common 
      adverse events (AEs) were hematologic and more frequent among Japanese patients 
      than the overall population (neutropenia: 93.8% [87.5% grade 3/4] vs 79.5% 
      [66.4%]; leukopenia: 62.5% [43.8%] vs 39.0% [24.8%]); no Japanese patients had 
      febrile neutropenia. Palbociclib dose reductions due to toxicity (mainly 
      neutropenia) were more common in Japanese patients (62.5% vs 36.0%); few 
      permanently discontinued due to AEs. Although mean palbociclib trough 
      concentration was higher in Japanese patients vs non-Asians (95.4 vs 61.7 ng/mL), 
      the range of individual values of the Japanese patients was within that of 
      non-Asians. CONCLUSIONS: These results from PALOMA-2 suggest that 
      palbociclib-letrozole merits consideration as a first-line treatment option for 
      postmenopausal Japanese patients with ER+/HER2‒ ABC. ClinicalTrials.gov: 
      NCT01740427.
FAU - Mukai, Hirofumi
AU  - Mukai H
AD  - Division of Breast and Medical Oncology, National Cancer Center Hospital East, 
      6-5-1 Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan. hrmukai@east.ncc.go.jp.
FAU - Shimizu, Chikako
AU  - Shimizu C
AD  - National Cancer Center Hospital, Tokyo, Japan.
FAU - Masuda, Norikazu
AU  - Masuda N
AD  - National Hospital Organization Osaka National Hospital, Osaka, Japan.
FAU - Ohtani, Shoichiro
AU  - Ohtani S
AD  - Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
FAU - Ohno, Shinji
AU  - Ohno S
AD  - The Cancer Institute Hospital of JFCR, Tokyo, Japan.
FAU - Takahashi, Masato
AU  - Takahashi M
AD  - National Hospital Organization Hokkaido Cancer Center, Hokkaido, Japan.
FAU - Yamamoto, Yutaka
AU  - Yamamoto Y
AD  - Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
FAU - Nishimura, Reiki
AU  - Nishimura R
AD  - Kumamoto Shinto General Hospital, Kumamoto, Japan.
FAU - Sato, Nobuaki
AU  - Sato N
AD  - Niigata Cancer Center Hospital, Niigata, Japan.
FAU - Ohsumi, Shozo
AU  - Ohsumi S
AD  - National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
FAU - Iwata, Hiroji
AU  - Iwata H
AD  - Aichi Cancer Center Hospital, Aichi, Japan.
FAU - Mori, Yuko
AU  - Mori Y
AD  - Pfizer Japan Inc, Tokyo, Japan.
FAU - Hashigaki, Satoshi
AU  - Hashigaki S
AD  - Pfizer Japan Inc, Tokyo, Japan.
FAU - Muramatsu, Yasuaki
AU  - Muramatsu Y
AD  - Pfizer Japan Inc, Tokyo, Japan.
FAU - Nagasawa, Takashi
AU  - Nagasawa T
AD  - Pfizer Japan Inc, Tokyo, Japan.
FAU - Umeyama, Yoshiko
AU  - Umeyama Y
AD  - Pfizer Japan Inc, Tokyo, Japan.
FAU - Lu, Dongrui R
AU  - Lu DR
AD  - Pfizer Oncology, San Diego, CA, USA.
FAU - Toi, Masakazu
AU  - Toi M
AD  - Kyoto University Graduate School of Medicine, Kyoto, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT01740427
GR  - None/Pfizer (US)/
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20181204
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Estrogen)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
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  - Asian People
MH  - Breast Neoplasms/*drug therapy/metabolism/*mortality
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Letrozole/administration & dosage
MH  - Middle Aged
MH  - Neutropenia/chemically induced
MH  - Piperazines/administration & dosage/pharmacokinetics
MH  - Proportional Hazards Models
MH  - Pyridines/administration & dosage/pharmacokinetics
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen
MH  - Treatment Outcome
PMC - PMC6399183
OTO - NOTNLM
OT  - Advanced breast cancer
OT  - HER2-
OT  - HR+
OT  - Japanese
OT  - Letrozole
OT  - Palbociclib
COIS- H. Mukai, C. Shimizu, M. Takahashi, R. Nishimura, and S. Ohsumi have no conflicts 
      of interest to report. N. Masuda has received honoraria from Chugai, AstraZeneca, 
      Pfizer, and Takeda and research funding from Chugai, AstraZeneca, Kyowa-Kirin, 
      MSD, Novartis, Pfizer, Eli Lilly, and Daiichi Sankyo. S. Ohtani has received 
      honoraria from Chugai and Eisai. S. Ohno has received honoraria from Chugai, 
      AstraZeneca, Eisai, Taiho, Novartis, Pfizer, Kyowa-Hakko Kirin, and Sanofi; and 
      research funding from Taiho, Chugai, and Daiichi Sankyo. Y. Yamamoto has received 
      honoraria from Pfizer. N. Sato has received honoraria from Chugai, AstraZeneca, 
      Eisai, Pfizer, and Taiho. H. Iwata has received honoraria and research funding 
      from Pfizer and AstraZeneca, and fees for promotional materials from AstraZeneca. 
      M. Toi has received honoraria from Novartis, MSD, Takeda, AstraZeneca, Taiho, 
      Chugai, Pfizer, Eisai, Eli Lilly, Kyowa-Hakko Kirin, and Genomic Health 
      Institute; research funding from Novartis, AstraZeneca, Taiho, Chugai, Pfizer, 
      and Eli Lilly; served as a consultant/independent contractor for Kyowa-Hakko 
      Kirin and on an advisory board for Genomic Health Institute. S. Hashigaki, Y. 
      Muramatsu, and T. Nagasawa are employees of Pfizer; D. Lu, Y. Mori, and Y. 
      Umeyama are employees of and stockholders in Pfizer.
EDAT- 2018/12/06 06:00
MHDA- 2019/05/30 06:00
PMCR- 2018/12/04
CRDT- 2018/12/06 06:00
PHST- 2018/06/12 00:00 [received]
PHST- 2018/10/03 00:00 [accepted]
PHST- 2018/12/06 06:00 [pubmed]
PHST- 2019/05/30 06:00 [medline]
PHST- 2018/12/06 06:00 [entrez]
PHST- 2018/12/04 00:00 [pmc-release]
AID - 10.1007/s10147-018-1353-9 [pii]
AID - 1353 [pii]
AID - 10.1007/s10147-018-1353-9 [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2019 Mar;24(3):274-287. doi: 10.1007/s10147-018-1353-9. Epub 
      2018 Dec 4.