Add-on bevacizumab ups hypertension risk in CRC patients

The addition of bevacizumab (BVZ) to the standard regimen for the treatment of advanced colorectal cancer (CRC) appears to increase the risk of cardiovascular events, suggest the results of a meta-analysis presented at the recent ASCO Gastrointestinal Cancers Symposium (ASCO GI 2023).

“When BVZ was used as an add-on therapy to FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimens for colorectal cancer, it was associated with about five times higher odds of developing hypertension (grade ≥3),” said the researchers, led by Akshit Chitkara from the University of California Riverside, US.

Chitkara and his team searched the databases of PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) and clinical trials, published from 1980 to March 2022, with BVZ as an add-on therapy reporting cardiovascular side effects.

Various guideline-directed chemotherapies were included in the full analysis control group and FOLFOX therapy in the subgroup analysis control group. The researchers used a random-effects model with Review Manager; p<0.05 was deemed significant.

A total of 17,807 patients (mean age 65 years) were included in the meta-analysis. Pooled analysis from 19 RCTs revealed a fourfold increase in the odds of hypertension (grade ≥3) in patients treated with BVZ compared to the control group (odds ratio [OR], 3.82, 95 percent confidence interval [CI], 3.35‒4.36; p<0.00001; I², 78 percent). [ASCO GI 2023, abstract 113]

Subgroup analysis confirmed these findings, showing fivefold higher odds of hypertension in the BVZ group versus the FOLFOX group (OR, 5.24, 95 percent CI, 4.06‒6.77; p<0.00001; I², 58 percent).

In contrast, previous RCTs reported the safety of BVZ as add-on therapy to the standard regimen, with no significant toxicity risk, according to Chitkara and colleagues.

“Our findings are important as they give vital information in assessing the risk-benefit ratio of adding BVZ, especially in a population with vascular comorbidities,” the researchers said.

“Now that we have established the statistical significance of hypertensive risk with BVZ, it will be interesting to see how these events can be prevented in patients treated for metastatic colorectal cancer. Dedicated RCTs are needed to confirm these findings,” they added.

BVZ is a recombinant humanized monoclonal IgG antibody commonly used as first- and second-line adjuvant therapy for patients with metastatic CRC. Recent guidelines point to the combination of three cytotoxic drug regimens FOLFOX along with BVZ as a first-line option.

“As we see an upward trend in using BVZ, it is crucial to analyse the side effects and potential toxicities,” said the researchers, noting that hypertension is a common adverse effect of BVZ.

“The prevailing hypothesis for the mechanism of BVZ-induced hypertension is an increase in vascular tone due to the inhibition of VEGF-mediated vasodilation. A persistent elevation of arterial blood pressure is generally asymptomatic, but unmanaged hypertension can lead to cardiovascular complications, encephalopathy, and subarachnoid haemorrhage,” they added.