Hypertension as a predictive biomarker in bevacizumab treatment for colorectal cancer patients

Abstract

Bevacizumab treatment is associated with an increased risk of hypertension (HTN), a potential marker for effectiveness. We aimed to assess whether grades 2-3 HTN during bevacizumab treatment was associated with increased overall survival (OS) or progression-free survival (PFS). One hundred and eighty-one patients with metastatic colorectal cancer (CRC), who were treated in our Department from January 2009-February 2011 were included. Bevacizumab was administered jointly with standard first- or second-line chemotherapy protocols. Blood pressure was measured before each treatment. HTN was graded using common toxicity criteria. There were 181 CRC patients. Grades 2-3 HTN developed in 81 patients (44.75 %) but not in 100 patients (55.25 %); no patient developed grades 4-5 HTN. Median follow-up was 15.2 months. HTN was associated with better OS in HTN-positive versus HTN-negative patients (median not reached vs. 36.8 months, p = 0.029) and better PFS (29.9 vs. 17.2 months, p = 0.024, respectively). Bevacizumab-related HTN may represent a biomarker for clinical benefit in metastatic colorectal cancer patients.

Angiotensin II type-1 receptor blockers enhance the effects of bevacizumab-based chemotherapy in metastatic colorectal cancer patients

“…The development of Bev-induced arterial HT has recently been suggested as a potential predictive marker. Certain studies have reported that HT may predict Bev treatment efficacy, regardless of the analyzed endpoint (OS, PFS, or response rate) (17)(18)(19)(20)(21). In the present study, second-line OS tended to be longer in patients developing HT.…”

Correlation of bevacizumab-induced hypertension and outcomes of metastatic colorectal cancer patients treated with bevacizumab: a systematic review and meta-analysis

“…Interestingly, many clinical trials have found that patients with mCRC treated with bevacizumab who developed hypertension had a better prognosis than those without hypertension [16-22]. These results were obtained through retrospective analysis of a relatively small dataset, but the findings are statistically significant and supported by other studies [6].…”

“…Among the seven trials selected, five [16,17,19,21,22] included relevant data. The pooled analysis showed that the occurrence of hypertension induced by bevacizumab also resulted in a statistically significant improvement in OS compared with no hypertension (HR = 0.50; 95% CI: 0.37–0.68, P <0.001; heterogeneity χ 2  = 5.12, P for heterogeneity = 0.275; I 2  = 21.9%) (Figure  3).…”

Current opinion on bevacizumab on endometrial cancer treatment

“…Briefly, according to systematic review and meta-analysis, the incidence of all grade hypertension in patients with solid tumors receiving bevacizumab was 23.6 (95% CI 20.5 --27.1) whereas the relative risk of developing high-grade hypertension was 5.28 (95% CI 4.15 --6.71) with an incidence of 7.9 (95% CI 6.1 --10.2) [45]. Interestingly multiple studies had noted that bevacizumab-induced hypertension was correlated with better oncologic response to treatment [46][47][48] and might serve as surrogate for anti-tumor efficacy of the agent [49]. Recently some genetic markers were studied to identify whether genetic variation in the VEGF pathway or in hypertension-associated genes could predict bevacizumab-induced hypertension.…”

“…The identification of biomarkers able to predict either the efficacy or toxicity of antiangiogenic drugs is a compelling need across all cancer types and recently genetic variants for bevacizumab-induced hypertension were validated in breast cancer setting. At the same time multiple studies in colorectal and glioblastoma cancer patients suggested that hypertension induced by VEGF antibody was correlated with better treatment outcome allowing the consideration of hypertension as a predictive biomarker of clinical response [48,[80][81][82]. Bevacizumab-related toxicities, particularly hypertension and thromboembolism, need to be carefully evaluated and balanced in relationship of the peculiar characteristics of EC patients often at high risk of cardiovascular events.…”