Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases.
Adult
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Bevacizumab
/ administration & dosage
Brain
/ diagnostic imaging
Brain Neoplasms
/ drug therapy
Breast
/ pathology
Breast Neoplasms
/ drug therapy
Carboplatin
/ administration & dosage
Female
Genotyping Techniques
Humans
Kaplan-Meier Estimate
Magnetic Resonance Imaging
Middle Aged
Polymorphism, Single Nucleotide
Progression-Free Survival
Trastuzumab
/ administration & dosage
Vascular Endothelial Growth Factor A
/ genetics
Bevacizumab
Brain metastases
Breast cancer
Journal
Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353
Informations de publication
Date de publication:
30 11 2020
30 11 2020
Historique:
received:
29
07
2020
accepted:
15
11
2020
entrez:
1
12
2020
pubmed:
2
12
2020
medline:
22
6
2021
Statut:
epublish
Résumé
We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases. We enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24-96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes. Thirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46-78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1-2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed. The combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation. NCT01004172 . Registered 28 October 2009.
Sections du résumé
BACKGROUND
We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases.
METHODS
We enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24-96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes.
RESULTS
Thirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46-78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1-2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed.
CONCLUSIONS
The combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation.
TRIAL REGISTRATION
NCT01004172 . Registered 28 October 2009.
Identifiants
pubmed: 33256829
doi: 10.1186/s13058-020-01372-w
pii: 10.1186/s13058-020-01372-w
pmc: PMC7706261
doi:
Substances chimiques
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
Bevacizumab
2S9ZZM9Q9V
Carboplatin
BG3F62OND5
Trastuzumab
P188ANX8CK
Banques de données
ClinicalTrials.gov
['NCT01004172']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
131Subventions
Organisme : South-Eastern Norway Regional Health Authority
ID : 2016102
Organisme : Norwegian Cancer Society
ID : 6817564
Organisme : South-Eastern Norway Regional Health Authority
ID : 2013069
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