PMID- 33794440
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20211025
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 148
DP  - 2021 May
TI  - Pembrolizumab plus eribulin in hormone-receptor-positive, HER2-negative, locally 
      recurrent or metastatic breast cancer (KELLY): An open-label, multicentre, 
      single-arm, phase Ⅱ trial.
PG  - 382-394
LID - S0959-8049(21)00125-8 [pii]
LID - 10.1016/j.ejca.2021.02.028 [doi]
AB  - BACKGROUND: Pembrolizumab has modest activity if used in patients with 
      hormone-receptor-positive (HR+), HER2-negative, previously treated metastatic 
      breast cancer (BC). Our study investigated whether there would be any clinical 
      benefit in combining chemotherapy with pembrolizumab in a similar patient 
      population. METHODS: This single-arm, phase Ⅱ trial enrolled women aged >/=18 years 
      with HR+, HER2-negative, inoperable, locally recurrent or metastatic BC. Patients 
      were previously treated with hormonal therapy and 1-2 chemotherapy regimens for 
      locally recurrent and/or metastatic BC. On each 21-day cycle, patients received 
      intravenous pembrolizumab 200 mg on day 1 and eribulin 1∙23 mg/m(2) on days 1 and 
      8. The primary endpoint was the clinical benefit rate. Analysis of safety and 
      activity was carried out in all patients who met the screening criteria and 
      received at least 1 dose of study treatment. The trial is registered at 
      ClinicalTrials.gov, NCT03222856. RESULTS: Of the 44 patients enrolled between 
      January 29 and October 17, 2018, clinical benefit was achieved in 25 (56∙8%, 95% 
      confidence interval [CI]: 41∙0-71∙7), objective response in 18 (40∙9%, 95% CI: 
      26∙3-56∙8), median progression-free survival was 6∙0 months (95% CI: 3∙7-8∙4), 
      and 1-year overall survival was 59∙1% (95% CI: 45∙8-76∙2). The most common 
      treatment-emergent adverse events (AEs) of any grade were neutropenia (20 
      [45∙5%]), anaemia (17 [38∙6%]), alopecia (19 [43∙2%]), asthenia (19 [43∙2%]), 
      diarrhoea (14 [31∙8%]), fatigue (14 [31∙8%]), and peripheral neuropathy (12 
      [27∙3%]). Serious AEs occurred in 14 (31∙8%) patients including febrile 
      neutropenia (3 [6∙8%]), neutropenia (2 [4∙5%]), fever (2 [4∙5%]) and peripheral 
      neuropathy (2 [4∙5%]). Immune-related AEs occurred in 11 (25∙0%) patients. One 
      (2∙3%) patient died of cardiac arrest unrelated to study treatment. CONCLUSION: 
      Pembrolizumab plus eribulin demonstrates encouraging antitumour activity in 
      patients with heavily pre-treated, HR+, HER2-negative, locally recurrent or 
      metastatic BC. The safety and tolerability of the combination is similar to 
      eribulin or pembrolizumab monotherapy.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Perez-Garcia, Jose M
AU  - Perez-Garcia JM
AD  - International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain; Medica 
      Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia 
      Innovation Research (MEDSIR), Barcelona, Spain.
FAU - Llombart-Cussac, Antonio
AU  - Llombart-Cussac A
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia 
      Innovation Research (MEDSIR), Barcelona, Spain; Hospital Arnau de Vilanova 
      Universidad Catolica de Valencia "San Vicente Martir"Valencia, Spain.
FAU - G Cortes, Maria
AU  - G Cortes M
AD  - Hospital Universitario Ramon y Cajal, Madrid, Spain.
FAU - Curigliano, Giuseppe
AU  - Curigliano G
AD  - European Institute of Oncology IRCCS, University of Milano, Milan, Italy.
FAU - Lopez-Miranda, Elena
AU  - Lopez-Miranda E
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia 
      Innovation Research (MEDSIR), Barcelona, Spain; Hospital Universitario Ramon y 
      Cajal, Madrid, Spain.
FAU - Alonso, Jose L
AU  - Alonso JL
AD  - Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain.
FAU - Bermejo, Begona
AU  - Bermejo B
AD  - Hospital Clinico de Valencia, INCLIVA, CIBERONC, Valencia, Spain.
FAU - Calvo, Lourdes
AU  - Calvo L
AD  - Complejo Hospitalario Universitario A Coruna (CHUAC), A Coruna, Spain.
FAU - Caranana, Vicente
AU  - Caranana V
AD  - Hospital Arnau de Vilanova, Valencia, Spain.
FAU - de la Cruz Sanchez, Susana
AU  - de la Cruz Sanchez S
AD  - Complejo Hospitalario de Navarra, Pamplona, Spain.
FAU - M Vazquez, Raul
AU  - M Vazquez R
AD  - MD Anderson Cancer Center, Madrid, Spain.
FAU - Prat, Aleix
AU  - Prat A
AD  - Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain; 
      Translational Genomics and Targeted Therapies Group, IDIBAPS, Barcelona, Spain; 
      Department of Medicine, University of Barcelona, Barcelona, Spain.
FAU - R Borrego, Manuel
AU  - R Borrego M
AD  - Hospital Universitario Virgen del Rocio, Sevilla, Spain.
FAU - Sampayo-Cordero, Miguel
AU  - Sampayo-Cordero M
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia 
      Innovation Research (MEDSIR), Barcelona, Spain.
FAU - Segui-Palmer, Miguel A
AU  - Segui-Palmer MA
AD  - Corporacio Sanitaria Sanitari Parc Tauli, Sabadell, Spain.
FAU - Soberino, Jesus
AU  - Soberino J
AD  - IOB, Institute of Oncology, QuironSalud Group, Barcelona, Spain.
FAU - Malfettone, Andrea
AU  - Malfettone A
AD  - Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia 
      Innovation Research (MEDSIR), Barcelona, Spain.
FAU - Schmid, Peter
AU  - Schmid P
AD  - Barts ECMC, Barts Cancer Institute, Queen Mary University of London, London, 
      United Kingdom; Barts Hospital NHS Trust, London, United Kingdom.
FAU - Cortes, Javier
AU  - Cortes J
AD  - International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain; Medica 
      Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia 
      Innovation Research (MEDSIR), Barcelona, Spain; Vall d'Hebron Institute of 
      Oncology (VHIO), Barcelona, Spain. Electronic address: jacortes@vhio.net.
LA  - eng
SI  - ClinicalTrials.gov/NCT03222856
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210329
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Furans)
RN  - 0 (Ketones)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - DPT0O3T46P (pembrolizumab)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - LR24G6354G (eribulin)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/metabolism/pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Furans/administration & dosage
MH  - Humans
MH  - Ketones/administration & dosage
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/metabolism/pathology
MH  - Prognosis
MH  - Receptor, ErbB-2/*metabolism
MH  - Receptors, Estrogen/*metabolism
MH  - Receptors, Progesterone/*metabolism
MH  - Survival Rate
OTO - NOTNLM
OT  - Eribulin
OT  - HR-positive/HER2-negative metastatic breast cancer
OT  - PD-L1
OT  - Pembrolizumab
COIS- Conflict of interest statement M.G., G.C., J.L.A., B.B., L.C., V.C., S.C.S., 
      R.M.V., M.R.B., and J.S. have nothing to declare. The authors declare the 
      following financial interests/personal relationships which may be considered as 
      potential competing interests: J.M.P.-G. reports to have a consulting role for 
      Roche, Lilly, and MEDSIR, and travel expenses from Roche. A.L.-C. reports 
      leadership for Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD, 
      intellectual property for MEDSIR and Initia-Research; reports to have a 
      consulting role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, 
      and GSK; to be part of speaker bureau for Lilly, AstraZeneca, and MSD; research 
      funding from Roche, Foundation Medicine, and Pierre-Fabre, Agendia; and travel 
      expenses from Roche, Lilly, Novartis, Pfizer, and AstraZeneca. E.L.-M. reports to 
      have a consulting role for MEDSIR. A.P. reports honoraria from Pfizer, Novartis, 
      Roche, MSD Oncology, Lilly, Daiichi Sankyo, Amgen, to have a consulting role for 
      Amgen, Roche, Novartis, Pfizer, Brystol-Myers Squibb, Boehringer, PUMA 
      Biotechnology, Oncolytics Biotech, Daiichi Sankyo, Abbvie, NanoString 
      Technologies; research funding to the Institution from Roche, Novartis, Incyte, 
      PUMA Biotechnology; to have intellectual property (PCT/EP2016/080056: HER2 AS A 
      PREDICTOR OF RESPONSE TO DUAL HER2 BLOCKADE IN THE ABSENCE OF CYTOTOXIC THERAPY; 
      WO/2018/096191. Chemoendocrine score (CES) Based on PAM50 for breast cancer with 
      positive hormone receptors with an intermediate risk of recurrence); travel 
      expenses from Daiichi Sankyo; other relationship with Oncolytics, Peptomyc S.L.; 
      and that an immediate family member is an employee of Novartis. M.S.-C. reports 
      honoraria from MEDSIR, Syntax for Science, and Nestle; to have a consulting role 
      for MEDSIR, Syntax for Science, and Nestle; to be part of speaker bureau for 
      MEDSIR, Syntax for Science, Roche; research funding from MEDSIR, Syntax for 
      Science, and Roche; and travel expenses from MEDSIR, Syntax for Science, and 
      Roche. M.A.S.-P. reports to have research funding to the Institution from Roche, 
      Novartis; honoraria from Roche, Pfizer, Novartis, Amgen, Eisai, MSD; and 
      non-financial support from Roche, Pfizer, Novartis, Amgen, Eisai. A.M. is a 
      full-time employee of MEDSIR. P.S. reports to have honoraria from Pfizer, 
      AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim; consulting or advisory 
      role from Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, 
      Bayer, Eisai, Celgene, Puma; and grant to institution from Roche, Genentech, 
      Oncogenex, Novartis. J.C. reports to have a consulting role for Roche, Celgene, 
      Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi 
      Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, GSK, 
      Leuko, Bioasis, and Clovis Oncology; honoraria from Roche, Novartis, Celgene, 
      Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, and Daiichi Sankyo; 
      research funding to the Institution from Roche, Ariad pharmaceuticals, 
      AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F.Hoffman-La 
      Roche, Guardanth health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C, 
      and Queen Mary University of London; and intellectual property of MEDSIR.
EDAT- 2021/04/02 06:00
MHDA- 2021/10/26 06:00
CRDT- 2021/04/01 20:14
PHST- 2021/01/22 00:00 [received]
PHST- 2021/02/01 00:00 [revised]
PHST- 2021/02/03 00:00 [accepted]
PHST- 2021/04/02 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/04/01 20:14 [entrez]
AID - S0959-8049(21)00125-8 [pii]
AID - 10.1016/j.ejca.2021.02.028 [doi]
PST - ppublish
SO  - Eur J Cancer. 2021 May;148:382-394. doi: 10.1016/j.ejca.2021.02.028. Epub 2021 
      Mar 29.