PMID- 37598677
OWN - NLM
STAT- MEDLINE
DCOM- 20240117
LR  - 20240412
IS  - 1423-0232 (Electronic)
IS  - 0030-2414 (Linking)
VI  - 102
IP  - 1
DP  - 2024
TI  - Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin 
      in Patients with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian 
      Cancer.
PG  - 9-16
LID - 10.1159/000533420 [doi]
AB  - INTRODUCTION: The release of tumor-associated antigens with cytotoxic 
      chemotherapy treatment may enhance the response to immune checkpoint blockade. 
      Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in 
      metastatic breast cancer (MBC), which may also enhance intratumoral vascular 
      remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed 
      cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum 
      tolerated dose and recommended phase II dose (RP2D) of eribulin in combination 
      with durvalumab, as well as the safety and preliminary antitumor activity of the 
      combination in patients with previously treated HER2-negative (HER2-) MBC and 
      recurrent ovarian cancer (ROC). METHODS: Cohorts of 3-6 patients with HER2- MBC 
      and ROC were treated in a modified 3+3 design. Eligible patients received 
      escalating doses of eribulin (1.1 mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with 
      durvalumab (1.12 g IV on day 1) in 21-day cycles until dose-limiting toxicity 
      (DLT), intolerable adverse events (AEs), disease progression, or other reasons 
      for withdrawal. PRIMARY ENDPOINT: the rate of DLTs during cycles 1 and 2 of 
      therapy. Secondary endpoints: AE rate, objective response rate (ORR), 
      progression-free survival (PFS), and OS. RESULTS: Nine patients with a median of 
      4 prior therapies for advanced disease were treated: 5 patients with HER2- MBC (1 
      with triple-negative disease and 4 with hormone-positive disease) and 4 patients 
      with ROC. The RP2D of eribulin was 1.4 mg/m2 in combination with durvalumab. 
      There were no DLTs experienced during the first two cycles of therapy. The most 
      common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white 
      blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, 
      and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 
      (hepatitis) after 5 cycles of treatment, for which patient came off study. Two 
      other patients discontinued study drug related to toxicity (neutropenia [n = 1], 
      hepatic toxicity [n = 1]). ORR was 55%, and 4 additional patients experienced 
      stable disease. All MBC patients exhibited a response to therapy. Median PFS was 
      6.2 months. Median OS was 15.0 months. CONCLUSION: The combination of eribulin at 
      a dose of 1.4 mg/m2 with standard dose durvalumab had a favorable AE profile in 
      patients with previously treated HER2- MBC and ROC. The early antitumor activity 
      observed in all MBC patients enrolled in the study suggests that further 
      investigation of this combination is warranted.
CI  - (c) 2023 S. Karger AG, Basel.
FAU - Landry, Chrystal A
AU  - Landry CA
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Blanter, Julia
AU  - Blanter J
AD  - The Tisch Cancer Institute at Mount Sinai, New York, New York, USA.
FAU - Ru, Meng
AU  - Ru M
AD  - Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
FAU - Fasano, Julie
AU  - Fasano J
AD  - The Tisch Cancer Institute at Mount Sinai, New York, New York, USA.
FAU - Klein, Paula
AU  - Klein P
AD  - The Tisch Cancer Institute at Mount Sinai, New York, New York, USA.
FAU - Shao, Theresa
AU  - Shao T
AD  - The Tisch Cancer Institute at Mount Sinai, New York, New York, USA.
FAU - Bhardwaj, Aarti
AU  - Bhardwaj A
AD  - The Tisch Cancer Institute at Mount Sinai, New York, New York, USA.
FAU - Tiersten, Amy
AU  - Tiersten A
AD  - The Tisch Cancer Institute at Mount Sinai, New York, New York, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20230818
PL  - Switzerland
TA  - Oncology
JT  - Oncology
JID - 0135054
RN  - 28X28X9OKV (durvalumab)
RN  - LR24G6354G (eribulin)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Polyether Polyketides)
RN  - 0 (Furans)
RN  - 0 (Ketones)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Breast Neoplasms/pathology
MH  - Receptor, ErbB-2/metabolism
MH  - Antibodies, Monoclonal/adverse effects
MH  - *Neutropenia
MH  - *Ovarian Neoplasms/drug therapy
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Polyether Polyketides
MH  - *Furans
MH  - *Ketones
OTO - NOTNLM
OT  - Eribulin
OT  - Immunotherapy
OT  - Metastatic breast cancer
OT  - Recurrent ovarian cancer
EDAT- 2023/08/21 00:41
MHDA- 2024/01/17 06:43
CRDT- 2023/08/20 18:23
PHST- 2023/05/24 00:00 [received]
PHST- 2023/07/20 00:00 [accepted]
PHST- 2024/01/17 06:43 [medline]
PHST- 2023/08/21 00:41 [pubmed]
PHST- 2023/08/20 18:23 [entrez]
AID - 000533420 [pii]
AID - 10.1159/000533420 [doi]
PST - ppublish
SO  - Oncology. 2024;102(1):9-16. doi: 10.1159/000533420. Epub 2023 Aug 18.