Efficacy and safety of bevacizumab-based combination therapy for treatment of patients with metastatic colorectal cancer

Abstract

AimThe use of bevacizumab in combination therapy is an emerging trend in metastatic colorectal cancer treatment. However, the clinical value of different combination types remains under debate. Thus, a meta-analysis of randomized controlled trials (RCTs) comparing bevacizumab-based combination therapy with monotherapy (therapy that uses one type of treatment, such as chemotherapy or surgery alone, to treat metastatic colorectal cancer) was performed, aiming to evaluate the safety and efficacy of bevacizumab-based combination therapy and to find a more beneficial combination.MethodsWe searched for clinical studies that evaluated bevacizumab-based combination therapy in metastatic colorectal cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR) and grade 3/4 treatment-related adverse events (AEs), HRs of overall survival (OS), and progression-free survival (PFS).ResultsEight RCTs were identified (n=3,424). Treatments included combinations of bevacizumab and oxaliplatin, fluorouracil, and leucovorin (FOLFOX4), combinations of bevacizumab and capecitabine and oxaliplatin, combinations of bevacizumab and fluorouracil/leucovorin, combinations of bevacizumab and irinotecan, fluorouracil, and leucovorin (IFL), and combinations of bevacizumab and capecitabine. Bevacizumab-based combination therapy showed higher ORR (RR: 1.40; 95% CI: 1.10–1.78; P=0.005), PFS (HR: 0.64; 95% CI: 0.55–0.73; P=0.000), and OS (HR: 0.82; 95% CI: 0.73–0.92; P=0.001) values than monotherapy. However, higher grade 3/4 treatment-related AEs (RR: 1.27; 95% CI: 1.15–1.41; P=0.000) were observed in combination therapy than in monotherapy.ConclusionThis meta-analysis showed that the addition of IFL to bevacizumab better benefits PFS and safety. Adding FOLFOX4 was associated with better ORR and OS. The efficacy and safety of an IFL–bevacizumab–FOLFOX4 combination should be given greater weight in future clinical trials, guidelines, and clinical practice.

Therapeutic Targeting of the Tumor Microenvironment

“…Most of the ongoing trials are currently focused on assessing the combination of anti-VEGF therapy with chemotherapeutic agents (215) or immunotherapies (216,217). A meta-analysis of randomized control trials comparing the effect of different chemotherapeutic drugs alone, or in combination with bevacizumab, in metastatic colorectal cancer showed a beneficial effect of the combination in extending OS, PFS, and ORR (218). However, many other trials have reported no clinical benefit in adding the anti-VEGF antibody to their combinations.…”

Colorectal peritoneal metastases: Optimal management review

“…Previous publications described no increase in survival using these agents after resectable or unresectable disease[64,66]. Conversely, a recent meta-analysis[67] on the different types of anti-VEGF antibody combination therapies has shown a significant improvement in progression-free survival, overall survival and response rate.…”

The Probe Based Confocal Laser Endomicroscopy (pCLE) in Locally Advanced Gastric Cancer: A Powerful Technique for Real–Time Analysis of Vasculature

“…According to a very recent systematic review and meta-analysis the addition of anti-VEGFR2 targeting agents to the first- or second-line chemotherapy could prolong patient's OS and PFS in advanced or metastatic gastric cancer (16). The study also highlighted the inefficacy of anti-VEGFA therapy in this type of tumor, unlike what observed in other type of cancers (53–56). Thus, to better characterize the quality of the gastric cancer-associated vasculature by pCLE may grant the possibility to predict which patients will be more likely to respond to anti-angiogenic therapy, sparing the others from costly ineffective treatments and side effects.…”