Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial

Abstract

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m2), leucovorin (20 mg/m2) bolus, and 5-fluorouracil intravenous infusion (500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

Efficacy and Safety of Bevacizumab in Metastatic Colorectal Cancer: Pooled Analysis From Seven Randomized Controlled Trials

“…Individual patient data were pooled from seven RCTs of bevacizumab in the first-line (AVF2107, NO16966, ARTIST, AVF0780, AVF2192, AGITG MAX) and second-line (E3200) treatment of mCRC (Table 1) [1][2][3][4][5][6]16]. Previously published phase II and III studies were selected based on (1) their design as RCTs evaluating chemotherapy with or without bevacizumab for mCRC; (2) the use of identical definitions and procedures for collecting patient baseline characteristics, along with primary and secondary efficacy endpoints and safety assessments; and (3) the ability to access individual patient information within study databases.…”

“…The data from this trial, AVF2107, showed that bevacizumab prolonged both overall survival (OS) and progression-free survival (PFS) when added to irinotecan, bolus fluorouracil, and leucovorin. Subsequently, data from additional randomized controlled trials (RCTs) have demonstrated the efficacy and safety profiles of bevacizumab among a wider variety of patients with mCRC, in combination with multiple backbone chemotherapy regimens, and in different treatment settings [2][3][4][5][6][7].…”

Efficacy and Safety of Bevacizumab in Chinese Patients with Metastatic Colorectal Cancer

“…In the subsequent NO16966 study of bevacizumab in combination with Oxa-CT (XELOX or FOLFOX4) for first-line treatment of mCRC patients (Saltz et al, 2008), the MAX study of bevacizumab in combination with capecitabine monotherapy or capecitabine and mitomycin for first-line treatment of mCRC patients, and the AVEX study of bevacizumab in combination with single-agent capecitabine therapy for first-line treatment of elderly mCRC patients (Cunningham et al, 2013), positive primary endpoint results were obtained. Similarly, the phase Ⅲ, randomized ARTIST study of first-line treatment of Chinese patients with mCRC confirmed that bevacizumab in combination with a modified IFL regimen significantly improved efficacy in comparison with the modified IFL regimen alone (Guan et al, 2011).…”

The Efficacy of Additional Bevacizumab to Cytotoxic Chemotherapy Regimens for the Treatment of Colorectal Cancer: An Updated Meta-Analysis for Randomized Trials

“…35 As aforementioned, the additional benefits of BEV were not consistent across trials. As for OS, no efficacy of additional BEV to CTX could be identified in several trials, including FLU + LEU, 22,23 IFL, 10 FOLFOX4, 30 and CAP 29,30 based chemotherapy regimens. However, after being stratified based on the CTX, the addition of BEV to FLU + LEU and FOLFOX based chemotherapy showed evident efficacy; its additional benefit was also evident in IFL-based chemotherapy after ignoring the trial 10 leading greatly heterogeneity, suggesting that prior surgery treatment for CRC maybe a main confounding factor; as for CAP-based chemotherapy regimens, both trials 29,30 identified no additional benefits of BEV.…”