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Impact of Cardiovascular Comorbidities on the Effectiveness and Safety of Bevacizumab in Older Patients with Metastatic Colorectal Cancer

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Abstract

Background

Cardiovascular comorbidities are not contraindications of bevacizumab for metastatic colorectal cancer.

Objective

We aimed to evaluate the impact of cardiovascular comorbidities before bevacizumab treatment on overall survival and cardiovascular safety in older patients with metastatic colorectal cancer.

Methods

A 2009–2015 cohort of patients with metastatic colorectal cancer aged ≥ 65 years administered first-line bevacizumab was extracted from the French healthcare reimbursement claims database. Baseline heart failure, hypertension, and venous/arterial thromboembolic events were identified. The 36-month overall survival rate was evaluated using the Kaplan–Meier method, and the impact of cardiovascular comorbidities on the 36-month overall survival using a time-dependent, multivariable, Cox proportional hazards model. The 36-month cumulative incidence of cardiovascular events, and the impact of cardiovascular comorbidities on the likelihood of cardiovascular events were evaluated using the Fine and Gray model, with death as a competing risk.

Results

We included 9222 patients (56.4% male; median age 73 years). Two-thirds (66.7%) had baseline cardiovascular comorbidities. The median 36-month overall survival was 20.4 [95% confidence interval (CI) 19.9–21.0] and 21.8 [95% CI 21.1–22.6] months in patients with and without cardiovascular comorbidities, respectively. Age ≥ 75 years, dependency in activities of daily living, radiotherapy, and another targeted therapy were identified as death risk factors, but not cardiovascular comorbidities. At 36 months, cardiovascular events had occurred in 60.2% [95% CI 58.9–61.4] and 44.1% [95% CI 42.3–45.9] of patients with and without cardiovascular comorbidities. Baseline venous thrombosis, female, three or more cardiovascular medications, another targeted therapy, and more than six bevacizumab injections were identified as risk factors for cardiovascular events.

Conclusions

In clinical practice, cardiovascular comorbidities before administering bevacizumab to older patients with metastatic colorectal cancer impacted the cardiovascular safety, but not overall survival. Unless they limit functional independency, older patients with cardiovascular comorbidities should be treated with bevacizumab under close monitoring.

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Authors and Affiliations

  1. Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD; CHU de Bordeaux, Pôle de santé publique, Service de pharmacologie médicale, 33000, Bordeaux, France

    Amandine Gouverneur, Francesco Salvo & Pernelle Noize

  2. Univ. Bordeaux, INSERM CIC-P 1401, Bordeaux PharmacoEpi, 33000, Bordeaux, France

    Clélia Favary, Jérémy Jové, Magali Rouyer & Emmanuelle Bignon

  3. Université de Limoges, Institut OMEGA HEALTH, Laboratoire VieSanté - UR 24134 (Vieillissement, Fragilité, Prévention, e-Santé); CHU de Limoges, Pôle HU de gérontologie clinique, Service de médecine gériatrique, 87042, Limoges, France

    Achille Tchalla

  4. Université de Paris Cité, Paris Cancer Institute CARPEM; Hôpital Européen Georges Pompidou, APHP, Service de gériatrie, 75015, Paris, France

    Elena Paillaud

  5. Université de Paris; Hôpital Saint-Louis, APHP, Service de gastroentérologie, 75010, Paris, France

    Thomas Aparicio

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  1. Amandine Gouverneur
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Correspondence to Pernelle Noize.

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Funding

This study was supported by a grant from the French Ministry of Health and managed by the French National Cancer Institute, INCa (Grant number: INCa-DGOS_11409). The funding source had no role in the design, methods, subject recruitment, data collections, analysis, and preparation of the paper.

Conflicts of interest/competing interests

Elena Paillaud declares consulting fees or participation on advisory boards for GSK, MSD, Pfizer, and Sandoz. Thomas Aparicio declares payment or honoraria for conferences from Amgen, Pierre Fabre, and Servier, support for attending meetings from MSD, and participation on advisory boards for Sirtec, Pierre Fabre, and MSD. Amandine Gouverneur, Clélia Favary, Jérémy Jové, Magali Rouyer, Emmanuelle Bignon, Francesco Salvo, Achille Tchalla, and Pernelle Noize have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

The study protocol was approved by the ‘Comité d’expertise pour les recherches, les études et les évaluations dans le domaine de la santé’ and ‘Commission Nationale de l’Informatique et des Libertés’.

Consent to participate

The requirement for informed consent was waived because the data were anonymous.

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Not applicable.

Availability of data and material

According to the principles of data protection and French regulations, the authors cannot publicly release the data from the ‘Système National des Données de Santé’ (SNDS). However, any person or structure, public or private, for-profit or non-profit can access SNDS data upon authorization from the ‘Commission Nationale de l’Informatique et des Libertés’ (i.e., the French Data Protection Office) to carry out a study, research, or an evaluation of public interest (https://www.snds.gouv.fr).

Code availability

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Authors’ contributions

AG, MR, FS, TA, and PN participated in the concept and design of the work; AG, MR, EB, and PN participated in the acquisition of data; CF and JJ participated in the analysis of the data and have directly accessed and verified the underlying data reported in the article; all authors participated in the interpretation of the data. AG and PN participated in drafting the work; all authors participated in revising it critically for important intellectual content. All authors give final approval of the version to be published.

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Gouverneur, A., Favary, C., Jové, J. et al. Impact of Cardiovascular Comorbidities on the Effectiveness and Safety of Bevacizumab in Older Patients with Metastatic Colorectal Cancer. Targ Oncol 18, 717–726 (2023). https://doi.org/10.1007/s11523-023-00986-2

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