Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Aug;26(8):1896-1907.
doi: 10.1007/s12094-024-03411-w. Epub 2024 Apr 5.

Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study

Álvaro Rodríguez-Lescure  1   2 , Javier Gallego  3 , Pilar Garcia-Alfonso  4 , Bartomeu Massuti  5 , Raúl Márquez  6   7 , Lourdes Calvo  6   8 , Pedro Sánchez-Rovira  6   9 , Antonio Antón  6   10 , José Ignacio Chacón  6   11 , Eva Ciruelos  6   12 , Jose Juan Ponce  6   5 , Ana Santaballa  6   13 , Manuel Valladares-Ayerbes  8   14 , María Rosario Dueñas  9 , Vicente Alonso  10 , Jorge Aparicio  13 , Sara Encinas  7 , Luis Robles  12 , María José Escudero  6 , Rosalía Caballero  6 , Susana Bezares  6 , Juan de la Haba-Rodriguez  6   15   16
Affiliations
Observational Study

Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study

Álvaro Rodríguez-Lescure et al. Clin Transl Oncol. 2024 Aug.

Abstract

Background: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT.

Methods: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels.

Results: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy.

Conclusions: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy.

Clinical trial registry: ClinicalTrials.gov Identifier: NCT01733628.

Keywords: Bevacizumab; Blood pressure; Metastatic breast cancer; Metastatic colorectal cancer.

PubMed Disclaimer

Conflict of interest statement

Rodríguez-Lescure A has received consultant or advisory role from Roche, Lilly, Pfizer, Novartis, Daiichi-Sankyo and Astra-Zeneca; Speaker’s bureau fees from Daiichi-Sankyo, Merck and Astra-Zeneca. Gallego J has received consultant or advisory role from Amgen, Astellas, Bayer, BMS, Eisai, Ipsen, Lilly, Merck, MSD, Pierre-Fabre, Roche, Servier and Veracyte; Speaker’s bureau fees from Amgen, Bayer, BMS, Ipsen, Lilly, Merck, MSD, Novartis and Servier; Educational grants from Amgen, Ipsen, Merck, Novartis, Pierre-Fabre and Roche. Garcia-Alfonso P has received consultant or advisory role fees and Speaker’s bureau fees from Amgen, Merck Serono, MSD, Lilly, Roche, Sanofi, Servier and Pierre Fabre. Massuti B has received consultant or advisory role from Roche, Boehringer Ingelheim, Astra Zeneca, Merck Serono and Janssen; Speaker’s bureau fees from Roche, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Sanofi/Regeneron, Janssen Oncology and Pfizer; Travel accommodations expenses from Roche, MSD and Astra Zeneca. Ponce J has received consultant or advisory role from Astra Zeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Roche and Seattle Genetics; Speaker’s bureau fees from Astra Zeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer and Seattle Genetics. Santaballa A has received consulting or advisory role fees from GSK, Clovis, MSD, Astra Zeneca, Pfizer, Novartis and Lilly; Speaker’s bureau fees from GSK, Clovis, MSD, Astra Zeneca, Pfizer, Novartis, Lilly and Pierre Fabre; Travel accommodations expenses from Pfizer and MSD. Valladares M has received consulting or advisory role fees from Amgen, Servier and Bayer; Speaker’s bureau fees from Merk, Amgen, Servier, Bayer, Roche and Celgene; Research funding from Amgen and Roche; Travel accommodations expenses from Roche, Merk, Amgen and Servier. Alonso V has received consulting or advisory role fees from Sanofi, Amgen, Merk, Servier and Novartis; Travel accommodations expenses from Roche and Merk. Aparicio J has received consultant or advisory role fees from Amgen, Bayer, Merck, Merck Sharp & Dohme, Pierre Fabre and Servier. The rest of authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
Consort diagram
Fig. 2
Fig. 2
A–D Progression-free survival according to the presence or absence of high blood pressure levels. A Whole population through any method of AHT measurement. B Whole population through 24-h Holter monitoring and according to the presence or absence of ≥10 mmHg in systolic blood pressure at C3. C MBC patients through any method of AHT measurement. D mCRC through any method of AHT measurement
Fig. 2
Fig. 2
A–D Progression-free survival according to the presence or absence of high blood pressure levels. A Whole population through any method of AHT measurement. B Whole population through 24-h Holter monitoring and according to the presence or absence of ≥10 mmHg in systolic blood pressure at C3. C MBC patients through any method of AHT measurement. D mCRC through any method of AHT measurement
Fig. 3
Fig. 3
A–C Definition of a hypertension-predictive score based on principal components (PC) analysis. A PC1 explains 83% of the information provided by the variables. B Strip chart, and C boxplot distribution of the 32 patients according to PC1
See this image and copyright information in PMC

References

    1. Zhu X, Wu S, Dahut WL, Parikh CR. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis. 2007;49(2):186–193. doi: 10.1053/j.ajkd.2006.11.039. - DOI - PubMed
    1. Scartozzi M, Galizia E, Chiorrini S, Giampieri R, Berardi R, Pierantoni C, Cascinu S. Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol. 2009;20(2):227–230. doi: 10.1093/annonc/mdn637. - DOI - PubMed
    1. Maitland ML, Moshier K, Imperial J, Kasza KE, Karrison T, Elliott W, et al. Blood pressure (BP) as a biomarker for sorafenib (S), an inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway. J Clin Oncol. 2006;24(18_suppl):2035. doi: 10.1200/jco.2006.24.18_suppl.2035. - DOI
    1. Maitland ML, Bakris GL, Black HR, Chen HX, Durand JB, Elliott WJ, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst. 2010;102(9):596–604. doi: 10.1093/jnci/djq091. - DOI - PMC - PubMed
    1. Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391–400. doi: 10.1038/nrd1381. - DOI - PubMed

Publication types

Associated data