PMID- 34414532
OWN - NLM
STAT- MEDLINE
DCOM- 20211013
LR  - 20240405
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 189
IP  - 3
DP  - 2021 Oct
TI  - Full population results from the core phase of CompLEEment-1, a phase 3b study of 
      ribociclib plus letrozole as first-line therapy for advanced breast cancer in an 
      expanded population.
PG  - 689-699
LID - 10.1007/s10549-021-06334-0 [doi]
AB  - PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with 
      hormone receptor-positive (HR +), human epidermal growth factor 
      receptor-2-negative (HER2-) advanced breast cancer (ABC), the largest current 
      trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patients 
      treated with </= 1 line of prior chemotherapy and no prior endocrine therapy for 
      ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 
      2.5 mg/day and additionally monthly goserelin/leuprolide in men and 
      pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients 
      with stable CNS metastases and an Eastern Cooperative Oncology Group performance 
      status of 2. Primary objectives were safety and tolerability, and secondary 
      objectives were efficacy and quality of life (QoL). RESULTS: Overall, 3,246 
      patients were evaluated (median follow-up 25.4 months). Rates of all-grade and 
      grade >/= 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, 
      respectively. Treatment-related discontinuations due to all grade and grade >/= 3 
      AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs 
      of special interest (AESI) were as follows: neutropenia (74.5%), increased 
      alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), 
      and QTcF prolongation (6.7%); corresponding values for grade >/= 3 AESI were 57.2%, 
      7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months 
      (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during 
      treatment. CONCLUSION: Safety and efficacy data in this expanded population were 
      consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of 
      ribociclib plus letrozole in the first-line setting for patients with HR + , 
      HER2- ABC. TRIAL REGISTRATION: linicalTrials.gov NCT02941926.
CI  - (c) 2021. The Author(s).
FAU - De Laurentiis, Michelino
AU  - De Laurentiis M
AUID- ORCID: 0000-0001-9009-1572
AD  - Division of Breast Medical Oncology, Department of Breast and Thoracic Oncology 
      Director, Istituto Nazionale Tumori IRCCS "Fondazione Pascale", Napoli, Italy. 
      m.delaurentiis@istitutotumori.na.it.
FAU - Borstnar, Simona
AU  - Borstnar S
AD  - Institute of Oncology Ljubljana, Ljubljana, Slovenia.
FAU - Campone, Mario
AU  - Campone M
AD  - Western Cancer Institute, Nantes, France.
FAU - Warner, Ellen
AU  - Warner E
AD  - Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
FAU - Bofill, Javier Salvador
AU  - Bofill JS
AD  - Virgen del Rocio University Hospital, Biomedicine Institute, Seville, Spain.
FAU - Jacot, William
AU  - Jacot W
AD  - Montpellier Cancer Institute, Montpellier, France.
FAU - Dent, Susan
AU  - Dent S
AD  - The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada.
AD  - Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.
FAU - Martin, Miguel
AU  - Martin M
AD  - Gregorio Maranon General University Hospital, GEICAM, Universidad Complutense, 
      CIBERONC, Madrid, Spain.
FAU - Ring, Alistair
AU  - Ring A
AD  - Royal Marsden Hospital NHS Foundation Trust, Sutton, UK.
FAU - Cottu, Paul
AU  - Cottu P
AD  - Curie Institute, Paris, France.
FAU - Lu, Janice
AU  - Lu J
AD  - USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
FAU - Ciruelos, Eva
AU  - Ciruelos E
AD  - University Hospital 12 de Octubre, Clara Campal Comprehensive Cancer Center (HM 
      CIOCC), Madrid, Spain.
FAU - Azim, Hamdy A
AU  - Azim HA
AD  - Faculty of Medicine, Cairo University, Cairo, Egypt.
FAU - Chatterjee, Sanjoy
AU  - Chatterjee S
AD  - Tata Medical Center, Kolkata, India.
FAU - Zhou, Katie
AU  - Zhou K
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Wu, Jiwen
AU  - Wu J
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Menon-Singh, Lakshmi
AU  - Menon-Singh L
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Zamagni, Claudio
AU  - Zamagni C
AD  - Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italia.
LA  - eng
SI  - ClinicalTrials.gov/NCT02941926
PT  - Clinical Trial, Phase III
PT  - Journal Article
DEP - 20210819
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Aminopyridines)
RN  - 0 (Purines)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - TK8ERE8P56 (ribociclib)
SB  - IM
EIN - Breast Cancer Res Treat. 2021 Oct 8;:. PMID: 34625861
MH  - Aminopyridines
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Breast Neoplasms/drug therapy
MH  - Female
MH  - Humans
MH  - Letrozole/therapeutic use
MH  - Purines
MH  - *Quality of Life
MH  - Receptor, ErbB-2
MH  - Receptors, Estrogen
MH  - Receptors, Progesterone
PMC - PMC8505291
OTO - NOTNLM
OT  - Advanced breast cancer
OT  - CDK4/6 inhibitor
OT  - Endocrine therapy
OT  - Ribociclib
COIS- Michelino De Laurentiis has received honoraria for consulting or advisory roles 
      from Amgen, AstraZeneca, Celgene, Eisai, Lilly, MSD, Novartis, Pfizer, Pierre 
      Fabre, and Roche; Honoraria: Amgen, AstraZeneca, Celgene, Eisai, Lilly, MSD, 
      Novartis, Pfizer, Pierre Fabre, and Roche; honoraria for participation in 
      speakers' bureau from Novartis; research funding from Bristol-Myers Squibb, 
      Daiichi Sankyo, Lilly, Novartis, MacroGenics, MSD, Pfizer, Puma Biotechnology, 
      and Roche. Simona Borstnar has received honoraria for consulting or advisory 
      roles from Amgen, AstraZeneca, Lilly, Novartis, Pfizer, and Roche; honoraria for 
      participation in speakers' bureaux from Amgen, Lilly, Krka, Novartis, Pfizer, and 
      Roche. Mario Campone has received honoraria for consulting or advisory roles from 
      AstraZeneca, Novartis, AbbVie, Sanofi, Lilly, Pfizer, Sandoz, Servier, Accord, 
      and Pierre Fabre; honoraria from Novartis and Lilly; honoraria for participation 
      in speakers' bureaux from Novartis and Lilly; reimbursement for travel, 
      accommodations, and expenses from Pfizer, Roche, and AstraZeneca. Ellen Warner 
      has received reimbursement for travel, accommodations, or expenses from Novartis. 
      Javier Salvador Bofill has received honoraria for consulting or advisory roles 
      from Roche, Novartis, Pfizer, and MSD; honoraria for participation in speakers' 
      bureaux from Novartis and Roche; honoraria from Novartis, Pfizer, and Roche; 
      reimbursement for travel, accommodations, or expenses from Roche, Novartis, and 
      Pfizer. William Jacot has received honoraria for consulting or advisory roles 
      from AstraZeneca, Eisai, Lilly France, MSD, Novartis, Pfizer, and Roche; research 
      funding from AstraZeneca; reimbursement for travel, accommodations, or expenses 
      from AstraZeneca, Chugai Pharma, Eisai, GlaxoSmithKline, and Lilly France. Susan 
      Dent has received honoraria for consulting or advisory roles from Novartis, 
      Pfizer, and Roche; honoraria from Eli Lilly, Novartis, and Roche; research 
      funding from Hoffman La-Roche, Novartis, and Pfizer; reimbursement for travel, 
      accommodations, or expenses from AstraZeneca. Miguel Martin has received 
      honoraria for consulting or advisory roles from Amgen, AstraZeneca, Eli Lilly, 
      Novartis, Pfizer, PharmaMar, Puma Biotechnology, Roche/Genentech, and Taiho 
      Oncology; honoraria for participation in speakers' bureaux from AstraZeneca, 
      Amgen, Roche/Genentech, Novartis, and Pfizer; research funding from Roche and 
      Novartis. Alistair Ring has received honoraria for consulting or advisory roles 
      from Pfizer and Roche; honoraria from AstraZeneca, Lilly, Novartis, Pfizer, and 
      Roche; research funding from AstraZeneca. Paul Cottu has received honoraria for 
      consulting or advisory roles from Novartis and Pfizer; research funding from 
      AstraZeneca, Genentech/Roche, Novartis, Pierre Fabre, and Pfizer; reimbursement 
      for travel, accommodations, or expenses from AstraZeneca, NanoString 
      Technologies, Novartis, Pfizer, and Roche. Janice Lu has received honoraria for 
      consulting or advisory roles from Pfizer, Novartis, and Puma. Eva Ciruelos has 
      received honoraria for consulting or advisory roles from Pfizer, Novartis, Lilly, 
      and Roche; honoraria from Pfizer, Novartis, Lilly, and Roche; honoraria for 
      participation in speakers' bureaux from Pfizer, Novartis, Lilly, and Roche; 
      reimbursement for travel, accommodations, or expenses from Pfizer and Roche. 
      Hamdy A. Azim has received honoraria for consulting or advisory roles from ASZ, 
      Bristol-Myers Squibb, Janssen, MSD, Novartis, Pfizer, Amgen, Lilly, and Roche; 
      employment by Innate France (immediate family member); honoraria from Amgen, ASZ, 
      Bristol-Myers Squibb, MSD, Novartis, Pfizer, and Roche; research funding from 
      Pfizer. Sanjoy Chatterjee has received honoraria for consulting or advisory roles 
      from Tata Medical Center. Katie Zhou is employed by Novartis. Jiwen Wu is 
      employed by Novartis. Lakshmi Menon-Singh is employed by Novartis. Claudio 
      Zamagni has received honoraria for consulting or advisory roles from AstraZeneca, 
      Eisai, Novartis, Pfizer, PharmaMar, Pierre Fabre, and Roche; research funding 
      from AbbVie, Array BioPharma, AstraZeneca, Celgene, Medivation, Morphotek, 
      Novartis, Pfizer, Roche, and Roche/Genentech; reimbursement for travel, 
      accommodations, or expenses from Celgene, Novartis, Pierre Fabre, and Roche.
EDAT- 2021/08/21 06:00
MHDA- 2021/10/14 06:00
PMCR- 2021/08/19
CRDT- 2021/08/20 07:17
PHST- 2020/12/07 00:00 [received]
PHST- 2021/07/14 00:00 [accepted]
PHST- 2021/08/21 06:00 [pubmed]
PHST- 2021/10/14 06:00 [medline]
PHST- 2021/08/20 07:17 [entrez]
PHST- 2021/08/19 00:00 [pmc-release]
AID - 10.1007/s10549-021-06334-0 [pii]
AID - 6334 [pii]
AID - 10.1007/s10549-021-06334-0 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2021 Oct;189(3):689-699. doi: 
      10.1007/s10549-021-06334-0. Epub 2021 Aug 19.