PMID- 36239405
OWN - NLM
STAT- MEDLINE
DCOM- 20230123
LR  - 20230204
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 28
IP  - 1
DP  - 2023 Jan 18
TI  - Palbociclib with Fulvestrant or Letrozole in Endocrine-Sensitive Patients with 
      HR-Positive/HER2-Negative Advanced Breast Cancer: A Detailed Safety Analysis of 
      the Randomized PARSIFAL Trial.
PG  - 23-32
LID - 10.1093/oncolo/oyac205 [doi]
AB  - BACKGROUND: Palbociclib has gained a central role in the treatment of hormone 
      receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) 
      advanced breast cancer (ABC). Despite its manageable toxicity profile, venous 
      thromboembolism (VTE) or interstitial lung disease (ILD)/pneumonitis may 
      infrequently occur. Therefore, we provide a comprehensive summary of the safety 
      and tolerability of the combination of endocrine therapy and palbociclib among 
      patients included in the randomized phase 2 PARSIFAL study. MATERIALS AND 
      METHODS: Patients with endocrine-sensitive HR+/HER2- ABC and no prior therapy in 
      an advanced setting (n = 486) were randomly assigned 1:1 to receive 
      fulvestrant-palbociclib (FP) or letrozole-palbociclib (LP). Laboratory tests and 
      the incidence of adverse events (AEs) were recorded at baseline and day 1 of each 
      cycle. Progression-free survival (PFS) was estimated for patients with and 
      without VTE. RESULTS: A total of 483 patients were analyzed. Neutropenia, 
      leukopenia, anemia, asthenia, arthralgia, fatigue, and diarrhea were the most 
      frequent AEs in both groups. Febrile neutropenia occurred in 3 (1.2%) patients of 
      the FP group and in 1 (0.4%) patient in the LP group. Six (2.5%; 0.4% grade 3) 
      patients in the FP group and 6 patients (2.5%; 0.4% grade 3) in the LP group 
      experienced ILD/pneumonitis. Pulmonary embolism was reported in 12 (5.0%) 
      patients in the FP group and 6 (2.5%) patients in the LP group. Advanced age at 
      baseline was the only factor significantly associated with an increased risk of 
      pulmonary embolism (P < .01). CONCLUSION: The PARSIFAL data confirmed the 
      favorable safety profile of both palbociclib regimens. VTE and ILD/pneumonitis 
      were occasionally reported, and their early detection allowed patients to 
      continue treatment effectively without detriment to efficacy. CLINICALTRIALS.GOV 
      IDENTIFIER: NCT02491983; https://clinicaltrials.gov/ct2/show/NCT02491983).
CI  - (c) The Author(s) 2022. Published by Oxford University Press.
FAU - Di Cosimo, Serena
AU  - Di Cosimo S
AD  - Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA.
FAU - Perez-Garcia, Jose Manuel
AU  - Perez-Garcia JM
AD  - International Breast Cancer Center (IBCC), Quironsalud Group, Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA.
FAU - Bellet, Meritxell
AU  - Bellet M
AD  - Vall d'Hebron University Hospital, Medical Oncology Department; Vall d'Hebron 
      Institute of Oncology (VHIO), Barcelona, Spain.
FAU - Dalenc, Florence
AU  - Dalenc F
AD  - Institut Claudius Regaud, IUCT-Oncopole, CRCT, Inserm, Department of Medical 
      Oncology, Toulouse, France.
FAU - Gil Gil, Miguel J
AU  - Gil Gil MJ
AD  - Institut Catala d'Oncologia, Breast Cancer Unit and Medical Oncology Department, 
      IDIBELL, L'Hospitalet, Barcelona, Spain.
FAU - Ruiz Borrego, Manuel
AU  - Ruiz Borrego M
AD  - Hospital Universitario Virgen del Rocio, Medical Oncology Department, Seville, 
      Spain.
FAU - Gavila, Joaquin
AU  - Gavila J
AD  - Fundacion Instituto Valenciano de Oncologia, Medical Oncology Department, 
      Valencia, Spain.
FAU - Sampayo-Cordero, Miguel
AU  - Sampayo-Cordero M
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood NJ, USA.
FAU - Aguirre, Elena
AU  - Aguirre E
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood NJ, USA.
FAU - Schmid, Peter
AU  - Schmid P
AD  - Barts ECMC, Barts Cancer Institute, Queen Mary University of London, and Barts 
      Hospital NHS Trust, London, UK.
FAU - Marme, Frederik
AU  - Marme F
AUID- ORCID: 0000-0002-6591-3367
AD  - Leitung Sektion Translationale Gynakologische Onkologie Nationales Centrum fur 
      Tumorerkrankungen und Universitatsfrauenklinik Heidelberg, Heidelberg, Germany.
FAU - Gligorov, Joseph
AU  - Gligorov J
AD  - Hospital Tenon (AP-HP), Medical Oncology Department, Paris, France.
FAU - Schneeweiss, Andreas
AU  - Schneeweiss A
AD  - Heidelberg University Hospital and German Cancer Research Center, National Center 
      for Tumor Diseases (NCT), Heidelberg, Germany.
FAU - Albanell, Joan
AU  - Albanell J
AD  - Hospital del Mar, Medical Oncology, Barcelona, Spain.
FAU - Zamora, Pilar
AU  - Zamora P
AD  - Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
FAU - Wheatley, Duncan
AU  - Wheatley D
AD  - Royal Cornwall Hospitals NHS Trust, Truro, UK.
FAU - Martinez-De Duenas, Eduardo
AU  - Martinez-De Duenas E
AD  - Hospital Provincial Castellon, Servicio de Oncologia, Castello De La Plana, 
      Spain.
FAU - Caranana, Vicente
AU  - Caranana V
AD  - Hospital Arnau de Vilanova, Valencia, Spain.
FAU - Amillano, Kepa
AU  - Amillano K
AD  - Hospital Universitari Sant Joan de Reus, Reus, Spain.
FAU - Mina, Leonardo
AU  - Mina L
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood NJ, USA.
FAU - Malfettone, Andrea
AU  - Malfettone A
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood NJ, USA.
FAU - Cortes, Javier
AU  - Cortes J
AUID- ORCID: 0000-0001-7623-1583
AD  - International Breast Cancer Center (IBCC), Quironsalud Group, Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA.
AD  - Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad 
      Europea de Madrid, Madrid, Spain.
FAU - Llombart-Cussac, Antonio
AU  - Llombart-Cussac A
AD  - Hospital Arnau de Vilanova, Valencia, Spain.
AD  - Universidad Catolica de Valencia San Vicente Martir, Valencia, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02491983
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 22X328QOC4 (Fulvestrant)
RN  - 7LKK855W8I (Letrozole)
RN  - G9ZF61LE7G (palbociclib)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - 0 (Receptors, Estrogen)
SB  - IM
MH  - Female
MH  - Humans
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - *Breast Neoplasms
MH  - Fulvestrant/therapeutic use
MH  - Letrozole/therapeutic use
MH  - *Pulmonary Embolism/etiology
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - *Venous Thromboembolism/etiology
PMC - PMC9847524
OTO - NOTNLM
OT  - advanced breast cancer
OT  - endocrine therapy
OT  - interstitial lung disease
OT  - neutropenia
OT  - palbociclib
OT  - pneumonitis
OT  - venous thromboembolism
COIS- Serena Di Cosimo: Novartis, Pierre-Fabre, IQVIA (fees for medical education), 
      Fondazione Associazione Italiana Ricerca contro il Cancro (RF, [AIRC 
      institutional grant IG 20774]), Medica Scientia Innovation Research (C/A, medical 
      advisor); Jose Manuel Perez-Garcia: Lilly, Roche, Eisai, Daiichi Sankyo, 
      AstraZeneca, Seattle Genetics (C/A), Roche (travel compensation), Medica Scientia 
      Innovation Research (E); Meritxell Bellet: Pfizer, Novartis, Lilly (C/A, H, 
      speaker's bureau), Pfizer, Roche (travel compensation); Miguel J. Gil-Gil: 
      Pfizer, Novartis, Eisai (H), Khern, Daiichi, Pfizer, Roche (travel compensation), 
      Daiichi, Agendia, Genomic Health (C/A); Manuel Ruiz-Borrego: Novartis, Pfizer, 
      Merck Sharp & Dohme Corp (C/A), Pfizer, Novartis, Roche, Lilly, AstraZeneca 
      (speaker's bureau); Joaquin Gavila: Pfizer, Novartis, Lilly, Merck Sharp & Dohme 
      Corp. (C/A), Pfizer, Novartis, Lilly, Roche (H), Roche (travel compensation), 
      Novartis, Pfizer (speaker's bureau); Miguel Sampayo-Cordero: Medica Scientia 
      Innovation Research, Syntax for Science, Roche (RF, travel compensation, 
      speaker's bureau), Medica Scientia Innovation Research, Syntax for Science, 
      Nestle (C/A, H), Medica Scientia Innovation Research (E); Elena Aguirre: Merck 
      Sharp & Dohme Corp, AstraZeneca, Pfizer, Roche (C/A); Peter Schmid: Pfizer, 
      AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, 
      Puma (C/A), Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim 
      (H), Roche, Genentech, Oncogenex, Novartis (RF [institutional grants]); Frederik 
      Marme: Roche/Genentech, Novartis, AstraZeneca, Eisai, Tesaro, Clovis, Merck Sharp 
      & Dohme Corp Oncology, Vaccibody (RF [institutional]), Roche, Pfizer, Novartis, 
      PharmaMar, AstraZeneca (travel compensation), and serving as a consultant to 
      Tesaro, Pfizer, Novartis, GenomicHealth, CureVac, Amgen, Celgene, Eisai, 
      Janssen-Cilag (C/A), AstraZeneca, Roche, Vaccibody, ImmunoMedics (C/A 
      [institutional]), Roche/Genentech, Novartis, Pfizer, AstraZeneca, Tesaro, Clovis 
      Oncology, Eisai, Celgene, Genomic Health, PharmaMar, Amgen, CureVac, Merck Sharp 
      & Dohme Corp Oncology, Janssen-Cilag, ImmunoMedics (H, to the institution); 
      Joseph Gligorov: Daiichi, Eisai, Genomic Health, Immunomedics, Ipsen, 
      Macrogenics, Merck Sharp & Dohme Corp, Mylan, Novartis, Onxeo, Pfizer, Roche 
      (C/A), Eisai, Genomic Health, Ipsen, Merck Sharp & Dohme Corp, Mylan, Novartis, 
      Pfizer, Roche (speaker's bureau), Eisai, Genomic Health, Roche (RF), Eisai, 
      Genomic Health, Merck Sharp & Dohme Corp, Mylan, Novartis, Pfizer, Roche (travel 
      compensation); Andreas Schneeweiss: Celgene, Roche, AbbVie, Molecular Partner 
      (RF), Roche, Celgene, Pfizer, AstraZeneca, Novartis, Merck Sharp & Dohme Corp, 
      Tesaro, Lilly (H), Roche, AstraZeneca (ET), Celgene, Roche (travel compensation); 
      Joan Albanell: Pfizer, Roche, Amgen, Merck Sharp & Dohme Corp, Lilly (C/A), 
      Medica Scientia Innovation Research, Roche, Seattle Genetics (RF), Roche, Pfizer 
      (speaker's bureau), Roche, Pfizer, Amgen, Merck Sharp & Dohme Corp, Lilly (travel 
      compensation), Biocartis (royalties), patents for EGFRmut licensed to Biocartis, 
      for InBiomotion (IP); Pilar Zamora: Roche (RF), Roche, Pfizer (travel 
      compensation); Duncan Wheatley: Pfizer, Roche, Lilly (C/A), Pfizer, Roche, 
      Daiichii Sankyo, Novartis, Lilly (H), Roche (travel compensation), Lilly, Pfizer, 
      Novartis (speaker's bureau), AstraZeneca (personal fees for work on advisory 
      board); Eduardo Martinez-De Duenas: Pfizer, Novartis (C/A), Pfizer (H), Roche 
      (travel compensation); Leonardo Mina: Medica Scientia Innovation Research (E); 
      Andrea Malfettone: Medica Scientia Innovation Research (E); Javier Cortes: Roche, 
      Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle 
      Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp 
      & Dohme, GlaxoSmithKline, Leuko, Bioasis, Clovis Oncology (C/A), Roche, Ariad 
      Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, 
      Eisai, Hoffmann-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur 
      Therapeutics, Puma C, Queen Mary University of London (RF), Roche, Novartis, 
      Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi 
      Sankyo (H), Medica Scientia Innovation Research (IP); Antonio Llombart-Cussac: 
      Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, Genomic Health, GlaxoSmithKline 
      (C/A), Lilly, AstraZeneca, Merck Sharp & Dohme Corp (speaker's bureau), Roche, 
      Foundation Medicine, Pierre-Fabre, Agendia (RF), Medica Scientia Innovation 
      Research, Initia-Research (IP), Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, 
      Merck Sharp & Dohme Corp. (leadership role), Roche, Lilly, Novartis, Pfizer, 
      AstraZeneca (travel compensation). Florence Dalenc, Vicente Caranana, and Kepa 
      Amillano indicated no financial relationships. (C/A) Consulting/advisory 
      relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) 
      Honoraria received; (OI) Ownership interests; (IP) Intellectual property 
      rights/inventor/patent holder; (SAB) Scientific advisory board.
EDAT- 2022/10/15 06:00
MHDA- 2023/01/21 06:00
PMCR- 2022/10/14
CRDT- 2022/10/14 08:13
PHST- 2022/06/20 00:00 [received]
PHST- 2022/08/17 00:00 [accepted]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2023/01/21 06:00 [medline]
PHST- 2022/10/14 08:13 [entrez]
PHST- 2022/10/14 00:00 [pmc-release]
AID - 6761067 [pii]
AID - oyac205 [pii]
AID - 10.1093/oncolo/oyac205 [doi]
PST - ppublish
SO  - Oncologist. 2023 Jan 18;28(1):23-32. doi: 10.1093/oncolo/oyac205.