PMID- 37890351
OWN - NLM
STAT- MEDLINE
DCOM- 20231130
LR  - 20231205
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 195
DP  - 2023 Dec
TI  - Clinical activity of nivolumab in combination with eribulin in HER2-negative 
      metastatic breast cancer: A phase IB/II study (KCSG BR18-16).
PG  - 113386
LID - S0959-8049(23)00688-3 [pii]
LID - 10.1016/j.ejca.2023.113386 [doi]
AB  - AIM: We evaluated the efficacy and safety of nivolumab and eribulin combination 
      therapy for metastatic breast cancer (BC) in Asian populations. METHODS: In this 
      parallel phase II study, adult patients with histologically confirmed 
      recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or 
      triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals 
      in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab 
      (360 mg) on day 1 plus eribulin (1.4 mg/m(2)) on days 1 and 8 every 3 weeks until 
      disease progression or intolerable toxicity. The primary endpoint was the 
      investigator-assessed 6-month progression-free survival (PFS) rate in each 
      subtype. Secondary endpoints included investigator-assessed objective response 
      rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 
      1.1, disease control rate, overall survival, and treatment toxicity. The 
      association between PD-L1 expression and efficacy was investigated. RESULTS: 
      Forty-five patients with HR+HER2- BC and 45 with TNBC were enroled. Their median 
      age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior 
      treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2- 
      and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 
      5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2- and TNBC groups, 
      respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 
      24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression 
      >/=1%) and PD-L1- tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in 
      TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; 
      the most common immune-related adverse events (AEs) were grades 1/2 
      hypothyroidism and pruritus. Five patients discontinued therapy because of 
      immune-related AEs. CONCLUSION: Nivolumab plus eribulin showed promising efficacy 
      and tolerable safety in previously treated HER2- metastatic BC. TRIAL 
      REGISTRATION: NCT04061863.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Kim, Se Hyun
AU  - Kim SH
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Seoul National University Bundang Hospital, Seoul National University College of 
      Medicine, Seongnam, South Korea.
FAU - Im, Seock-Ah
AU  - Im SA
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University, College of Medicine, Seoul, South 
      Korea.
FAU - Suh, Koung Jin
AU  - Suh KJ
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Seoul National University Bundang Hospital, Seoul National University College of 
      Medicine, Seongnam, South Korea.
FAU - Lee, Kyung-Hun
AU  - Lee KH
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University, College of Medicine, Seoul, South 
      Korea.
FAU - Kim, Min Hwan
AU  - Kim MH
AD  - Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer 
      Center, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Sohn, Joohyuk
AU  - Sohn J
AD  - Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer 
      Center, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Park, Yeon Hee
AU  - Park YH
AD  - Hematology-Oncology, Samsung Medical Center Sungkyunkwan University School of 
      Medicine, Seoul, South Korea.
FAU - Kim, Ji-Yeon
AU  - Kim JY
AD  - Hematology-Oncology, Samsung Medical Center Sungkyunkwan University School of 
      Medicine, Seoul, South Korea.
FAU - Jeong, Jae Ho
AU  - Jeong JH
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, South Korea.
FAU - Lee, Kyoung Eun
AU  - Lee KE
AD  - Department of Hematology and Oncology, Ewha Womans University Hospital, Seoul, 
      South Korea.
FAU - Choi, In Sil
AU  - Choi IS
AD  - Department of Internal Medicine, Seoul Metropolitan Government Seoul National 
      University Boramae Medical Center, Seoul, South Korea.
FAU - Park, Kyong Hwa
AU  - Park KH
AD  - Division of Medical Oncology/Hematology, Department of Internal Medicine, Korea 
      University Anam Hospital, Seoul, South Korea.
FAU - Kim, Hee-Jun
AU  - Kim HJ
AD  - Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, 
      South Korea.
FAU - Cho, Eun Kyung
AU  - Cho EK
AD  - Division of Medical Oncology, Department of Internal Medicine, Gil Medical 
      Center, Gachon University College of Medicine, Incheon, South Korea.
FAU - Park, So Yeon
AU  - Park SY
AD  - Department of Pathology, Seoul National University Bundang Hospital, Seoul 
      National University College of Medicine, Seongnam, South Korea.
FAU - Kim, Milim
AU  - Kim M
AD  - Department of Pathology, Seoul National University Bundang Hospital, Seoul 
      National University College of Medicine, Seongnam, South Korea; Department of 
      Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, 
      South Korea.
FAU - Kim, Jee Hyun
AU  - Kim JH
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Seoul National University Bundang Hospital, Seoul National University College of 
      Medicine, Seongnam, South Korea. Electronic address: jhkimmd@snu.ac.kr.
LA  - eng
SI  - ClinicalTrials.gov/NCT04061863
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231014
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (B7-H1 Antigen)
RN  - LR24G6354G (eribulin)
RN  - 31YO63LBSN (Nivolumab)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - B7-H1 Antigen
MH  - *Breast Neoplasms/pathology
MH  - Nivolumab/therapeutic use
MH  - Receptor, ErbB-2/metabolism
MH  - *Triple Negative Breast Neoplasms/drug therapy
MH  - Aged
OTO - NOTNLM
OT  - Advanced breast cancer
OT  - Clinical trial
OT  - Eribulin
OT  - Immune checkpoint inhibitors
OT  - Luminal breast cancer
OT  - Metastatic breast cancer
OT  - Nivolumab
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Ono Pharmaceutical Co. provided the study drug (nivolumab) and 
      provided funding to Seoul National University Bundang Hospital for study conduct. 
      Eisai Korea inc. provided the study drug (eribulin) for study conduct. The 
      companies were not involved in trial data analysis and manuscript writing. SHK 
      has a consulting or advisory role with Ono Pharmaceutical. SI reports receiving 
      research grant from AstraZeneca, Daewoong Pharm, Eisai, Roche, and Pfizer and 
      personal consultation fees from AstraZeneca, Eisai, GSK, Hanmi, Lilly, MSD, 
      Idience, Novartis, Roche, and Pfizer. The research group received drugs from 
      Eisai and Boryung. KL reports receiving honorarium from AstraZeneca, 
      Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, Roche. JS reports receiving research 
      funding from MSD, Roche, Novartis, Lilly, Pfizer, Daiichi Sankyo, AstraZeneca, 
      GlaxoSmithKline, Sanofi, and Boehringer Ingelheim. KHP has a consulting or 
      advisory role with Eisai, Eli Lilly, Novartis, Daiichi Sankyo/Astra Zeneca, 
      Pfizer, IMBDx, Celltrion and Roche and has received research funding from Astra 
      Zeneca. JHK has a consulting or advisory role with Bixink, Eisai, Yuhan, 
      Novartis, Daiichi Sankyo/Astra Zeneca, Pfizer, and Roche and has received 
      research funding from Ono Pharmaceutical and Roche. All remaining authors have 
      declared no conflicts of interest.
EDAT- 2023/10/28 11:42
MHDA- 2023/11/27 12:43
CRDT- 2023/10/27 18:08
PHST- 2023/07/10 00:00 [received]
PHST- 2023/09/13 00:00 [revised]
PHST- 2023/10/06 00:00 [accepted]
PHST- 2023/11/27 12:43 [medline]
PHST- 2023/10/28 11:42 [pubmed]
PHST- 2023/10/27 18:08 [entrez]
AID - S0959-8049(23)00688-3 [pii]
AID - 10.1016/j.ejca.2023.113386 [doi]
PST - ppublish
SO  - Eur J Cancer. 2023 Dec;195:113386. doi: 10.1016/j.ejca.2023.113386. Epub 2023 Oct 
      14.