Tolerability on Serious Adverse Events of First-Line Bevacizumab and Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

Proper medication management is crucial in metastatic colorectal cancer because of its substantially low survival rate. There has been advancing evidence on the efficacy of the two most prescribed targeted agents (bevacizumab and cetuximab); however, comprehensive analyses on their safety are limited. This study aims to comprehensively assess the clinical safety of first-line bevacizumab and cetuximab-based chemotherapy in unresectable RAS wild-type metastatic colorectal cancer patients and to provide guidance on the selection of appropriate targeted therapeutic agents. Keyword searches of MEDLINE, Cochrane Library, and ClinicalKey were conducted per PRISMA guidelines. We performed pooled analysis on safety outcomes from six studies which administered FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) as backbone chemotherapy. Thirty different adverse events from six categories were compared. First-line bevacizumab-based chemotherapy substantially lowered the risks of adverse events related to the dermatological (RR 0.24, 95% CI: 0.11–0.53, p < 0.00001) and renal systems (RR 0.57, 95% CI: 0.37–0.86, p = 0.007), while significantly increasing the incidence of cardiovascular adverse events (RR 4.65, 95% CI: 1.83–11.78, p = 0.001). Thus, first-line cetuximab-based chemotherapy increases patient susceptibility to dermatological and renal adverse events, especially with rash and electrolyte disorders, whereas bevacizumab-based chemotherapy increases cardiovascular risks such as hypertension and arrhythmia.

Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis

“…Similar to the results from a previous meta-analysis on the tolerability on SAE of first-line bevacizumab and cetuximab for RAS wild-type metastatic CRC patients [ 37 ], the highest risk of serious HTN was observed in bevacizumab-based chemotherapy (RR 1.00; reference) over cetuximab- (RR 0.05; 95% CI 0.00–0.85) and panitumumab-based chemotherapy (RR 0.07; 95% CI 0.01–0.55); the RR of HTN was insignificant between second-line bevacizumab- and panitumumab-based chemotherapy. However, caution is advised with the interpretation of safety assessment results of second-line targeted treatment as it was evaluated with only one RCT [ 32 ], which demonstrated 4 and 0 cases of serious HTN (Grade 3 or 4 per CTCAE) in patients on bevacizumab- and cetuximab-based chemotherapy, respectively.…”

“…Skin toxicities, including acneiform skin rash and nail disorders, are well-known AEs of EGFR inhibitors [ 35 ], and previous meta-analysis from our research group also suggested higher risk of skin toxicities with cetuximab over bevacizumab [ 37 ]. This study revealed a significantly greater risk of serious dermatitis or paronychia with EGFR inhibitors, cetuximab and panitumumab.…”

Cost-effectiveness of FOLFOX6+Bevacizumab Versus FOLFOX6+Cetuximab in Stage IV Colorectal Cancer Patients in Shiraz, Iran

“…As a result, the absenteeism of the patients and their companions from work in this group was more than that in the group under treatment with FOLFOX6+Cetuximab. Furthermore, due to the fact that the side effects of FOLFOX6+Bevacizumab are usually greater and more severe than FOLFOX6+Cetuximab, and since chemotherapy by Bevacizumab increases the risk of cardiovascular diseases such as increased blood pressure and irregular heartbeat, 57 the cost of changes in the home environment for the adaptation of these patients was higher (approximately 2.5 times). These could have caused an increase in direct non-medical and indirect costs in the group receiving FOLFOX6+Bevacizumab.…”