Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness

Abstract

Introduction Targeting angiogenesis in metastatic colorectal cancer (mCRC) using bevacizumab is a standard of care. The addition of this targeted biological agent to first-line infusional fluoropyrimidine-based chemotherapy was associated with superior overall survival (OS) in several randomized and controlled studies for CRC patients in the metastatic setting. However, access to this therapy in countries with limited resources is challenging. In Morocco, bevacizumab was introduced for this indication after considerable efforts of the Ministry of Health and Lalla Salma Foundation to support cancer patients with a limited income. In this report, the real-world efficacy and safety of the combination of bevacizumab with chemotherapy in mCRC are reported based on a retrospective cohort in Eastern Morocco. Material and methods The archives of the medical records of 98 mCRC patients treated with first-line bevacizumab at the Hassan II Regional Cancer Center (Oujda, Morocco) were sampled from 1 st January 2014 to 31 st December 2019 and analyzed using descriptive statistics, Kaplan-Meier estimation, and a multivariable Cox regression model for a time-to-event study. Results The toxicity profile was dominated by grade I–II proteinuria (10%), bleeding events (10%), thromboembolic events (9%), grade I–III hypertension (3%), and other rare events such as delayed healing of the stoma, scar dehiscence, intestinal perforation, and heart failure deterioration. In terms of survival, median OS and progression-free survival in the whole cohort were 22 and 13 months respectively. Patients who benefited from a metastasectomy after bevacizumab treatment had 31 months of median OS as compared to 14 months in the matched cohort with non-resectable liver metastasis. Notably, we demonstrated that tumor sidedness is a predictive factor of OS [hazard ratio (HR) = 2.452; 95% CI: 1.434–4.191, p = 0.001]. Moreover, the median OS for patients who received between 10 and 20 or more than 20 bevacizumab administrations was 24 and 33 months respectively as compared to those who received less than 10 cures (17 months) (log rank p < 0.0001). These markedly improved outcomes were also confirmed in multivariate Cox regression. A highly significant association of bevacizumab use and OS was found after adjusting for covariates (HR = 0.518, 95% CI: 0.374–0.717; p < 0.0001). Conclusions The current study confirmed the important place of this therapeutic strategy in mCRC. Additional studies with prospective enrollment are awaited to validate these findings.

The Safety and Effectiveness of Bevacizumab in Metastatic Colorectal Cancer With Unresectable Metastases: A Real-Life Study From the South of Morocco

“…In our study, the left side accounted for 83.2% of cases, while the right side represented only 16.6% of cases. These findings align with the results of other studies [ 12 , 14 ].…”

The safety and effectiveness of Bevacizumab in Metastatic Colorectal Cancer with Unresectable Metastases: A Real-Life Study from the south of Morocco

“…(15) In our study, the left side accounts for 83.2%, while the right side represents only 16.6% of cases. These ndings align with the results of other studies ( 12) (14).…”

“…The median age within our population is 55 years old. A similar median age of 52 was found in a study carried out in the eastern region of Morocco, speci cally in Oujda (14).…”

“…A recent meta-analysis comprising 21 studies indicated that treatments based on bevacizumab are more effective in patients with left-sided mCRC in comparison to those with right-side tumors. Moreover, right-sided CRC is typically characterized by poorly differentiated, mucinous, signet ring histology with microsatellite instability and a mutation in RAS/RAF, in contrast to the left side (14).…”

Bevacizumab is associated with cerebral microstructural alterations: a DTI study in high-grade glioma

“…Taken together, prolonging PFS and therefore ideally prolonging the time to the loss of personal and economic independence is a worthwhile ambition for the therapeutic team. The systemic toxicity profile is well described and mostly manageable with proteinuria, bleeding, and thrombembolic events, and also hypertension as most frequent adverse events ( 46 ).…”