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| Home > Articles > Published articles > Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer : |
(Hospital Universitario Quiron. Medical Oncology Department) (Hospital Universitario 12 de Octubre (Madrid)) (Universidad Autónoma de Madrid. Facultad de Medicina) (Vall d'Hebron Institut d'Oncologia)| Date: | 2020 |
| Abstract: | 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 T 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 T 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 T cells both systemically and in tumor tissue. The magnitude of this benefit should be addressed in a randomized setting. (www. clinicaltrials. gov):. Registered on June 16, 2020. |
| Grants: | Ministerio de Economía, Industria y Competitividad PI16/00354 Ministerio de Economía, Industria y Competitividad PIE15/00068 Instituto de Salud Carlos III PI17/01865 Agencia Estatal de Investigación SAF2017-83732-R |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Durvalumab ; Bevacizumab ; HER2-negative breast cancer ; Vascular normalization ; Immuno-priming |
| Published in: | Breast cancer research, Vol. 22 (november 2020) , ISSN 1465-542X |
