Efficacy and safety of bevacizumab in combination with oxaliplatin, irinotecan and fluoropyrimidine-based therapy in advanced colorectal cancer

Abstract

Background: Bevacizumab is an anti-VEGF, humanized mAb that is the most advanced agent of its class in clinical development. Several studies have examined bevacizumab in combination with chemotherapy in the first- and second-line settings in patients with metastatic CRC. Despite of that, there is lack of information concerning the extent to which bevacizumab can be used to treat metastatic CRC. We still need more evidence related to efficacy and safety of bevacizumab in different settings, or sequential treatments. The aim of this study was to investigate efficacy and safety of bevacizumab added to different chemotherapy in patients with metastatic CRC. Methods: This was a controlled, prospective, multicentre, cohort study. Thirty patients with advanced colorectal cancer were enrolled into this study. Bevacizumab was applied with oxaliplatin-, irinotecan-, 5FU- or capecitabine -based chemotherapy in the first-, second- or third-therapy lines. Totally 261 cycles were applied. The median number of applied cycles per patient was 8 (range 2-16). Results: Objective tumor response (RR) was seen in 11 patients 37% (95%CI 19-69%) calculated on an intention-to-treat basis. The median duration of response was 12 months. Three of 11 patients (27%) with PR had secondary surgery. RR was seen in 9 of 16 patients (56%) who received bevacizumab in the first-line treatment and in 2 of 14 patients (14%) who received therapy in the second+ lines (p=0.02). Clinical benefit (PR+SD) was seen in 22 (74%) patients. 75% of patients achieved clinical benefit in the first-line and 74% in the second+ chemotherapy lines. The median time to progression (TTP) of the patients is was 9 + months (95%CI 7 - + ∞) at the moment of this analysis. The median TTP of patients who received bevacizumab in the first line was 11 months (95%CI 8 - + ∞). The median TTP of patients who received bevacizumab in the second+ lines was 5.5 months (95%CI 4 - + ∞) (p=0.015). The median survival time (OS) for all patients was 9 + months (95%CI 7 - + ∞). The median OS at the moment of analysis was 11 months (95%CI 9 - + ∞) for patients receiving bevacizumab in the first line, and 7 months for patients receiving the drug in the second+ lines (95%CI 6 - + ∞) (p=0.024). The incidence of any toxicity grade 3-4 was less than 10%. Bevacizumab associated incidence of grade 3-4 side effects did not exceed 5%. Hypertension 5% and thromboembolism 5% were the most frequent events. Gastrointestinal perforation did not occur. There was one toxic death due to sepsis and not directly associated with bevacizumab toxicity. Conclusion: Bevacizumab can safely be added to different chemotherapeutic regimens in first- and second+ line. The conferred benefit in overall survival, TTP and response rate obviously requires randomized trials

The addition of bevacizumab to fluoropyrimidine, irinotecan and oxaliplatin-based therapy improves survival for patients with metastatic colorectal cancer (CRC): Combined analysis of efficacy

“…Bevacizumab can be used not only in the first chemotherapy line. In some studies bevacizumab has been also used for patients who receive chemotherapy in the second or following chemotherapy lines 9,16 . The results of our study performed in Serbia suggest that bevacizumab should be used upfront rather than in second-line 9 .…”

“…Thus far, only one study with bevacizumab has been performed in Serbia 9 . The aim of this study was to investigate efficacy and safety of bevacizumab added to different chemotherapy in patients with metastatic CRC.…”

Biochemical liver function tests parameters do not indicate any difference in the degree of hepatotoxicity in patients with metastatic colorectal carcinoma treated with conventional anticancer drugs regardless the use of bevacizumab

“…Bevacizumab is one of the newer monoclonal antibodies used as an additional treatment to current anticancer drugs in patients with mCRC. The results of so far clinical studies show that bevacizumab increased the therapeutic effect of 5-FU and oxaliplatin leading to the significant clinical improvement [9][10][11][12][13][14][15][16] . These findings were confirmed in our study, where the largest number of patients with complete and partial responses belong to the group of patients additionally treated with bevacizumab.…”

“…The results of several clinical studies have shown that the addition of bevacizumab to conventional anticancer drugs [5fluorouracil (5-FU), oxaliplatin, irinotecan, capecitabine)] greatly contributed to their therapeutic effect [9][10][11][12][13][14][15][16] . However, there were no data on its influence on the increased values of liver function tests parameters.…”