2026-04-29T04:00:28Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/125352024-11-29T20:20:20Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Holgado, Esther
author
Manso, Luis
author
Morales, Serafin
author
Bermejo, Begoña
author
Colomer, Ramon
author
Apala, Juan V
author
Blanco, Raquel
author
Muñoz, Manuel
author
Caleiras, Eduardo
author
Iranzo, Vega
author
Martinez, Mario
author
Dominguez, Orlando
author
Hornedo, Javier
author
Gonzalez-Cortijo, Lucia
author
Cortes, Javier
author
Gasol Cudos, Ariadna
author
Malon, Diego
author
Lopez-Alonso, Antonio
author
Moreno-Ortíz, María C
author
Mañes, Santos
author
Quintela Fandino, Miguel Angel
author
Mouron, Silvana Andrea
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
CRIS contra el Cáncer
funder
AstraZeneca
2021-04-07T06:54:30Z
2021-04-07T06:54:30Z
2020-11-11
Breast Cancer Res . 2020;22(1):124.
http://hdl.handle.net/20.500.12105/12535
33176887
10.1186/s13058-020-01362-y
1465-542X
Breast cancer research : BCR
Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangiogenic bevacizumab after bevacizumab monotherapy for advanced HER2-negative breast cancer.
Patients had advanced HER2-negative disease that progressed while receiving single-agent bevacizumab maintenance as a part of a previous chemotherapy plus bevacizumab regimen. Treatment consisted of bi-weekly durvalumab plus bevacizumab (10 mg/kg each i.v.). Peripheral-blood mononuclear cells (PBMCs) were obtained before the first durvalumab dose and every 4 weeks and immunophenotyped by flow-cytometry. A fresh pre-durvalumab tumor biopsy was obtained; gene-expression studies and immunohistochemical staining to assess vascular normalization and characterize the immune infiltrate were conducted. Patients were classified as "non-progressors" if they had clinical benefit (SD/PR/CR) at 4 months. The co-primary endpoints were the changes in the percentage T cell subpopulations in PBMCs in progressors versus non-progressors, and PFS/OS time.
Twenty-six patients were accrued. Median PFS and OS were 3.5 and 11 months; a trend for a longer OS was detected for the hormone-positive subset (19.8 versus 7.4 months in triple-negatives; P = 0.11). Clinical benefit rate at 2 and 4 months was 60% and 44%, respectively, without significant differences between hormone-positive and triple-negative (P = 0.73). Non-progressors' tumors displayed vascular normalization features as a result of previous bevacizumab, compared with generally abnormal patterns observed in progressors. Non-progressors also showed increased T-effector and T-memory signatures and decreased TREG signatures in gene expression studies in baseline-post-bevacizumab-tumors compared with progressors. Notably, analysis of PBMC populations before durvalumab treatment was concordant with the findings in tumor samples and showed a decreased percentage of circulating TREGs in non-progressors.
This study reporting on sequential bevacizumab+durvalumab in breast cancer showed encouraging activity in a heavily pre-treated cohort. The correlative studies agree with the preclinical rationale supporting an immunopriming effect exerted by antiangiogenic treatment, probably by reducing TREGs cells both systemically and in tumor tissue. The magnitude of this benefit should be addressed in a randomized setting.
(www.clinicaltrials.gov): NCT02802098 . Registered on June 16, 2020.
eng
THERAPY
PROLIFERATION
NORMALIZATION
PROGRESSION
EXPRESSION
1ST-LINE
VEGF
Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial.
journal article
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