Maintenance single-agent bevacizumab or observation after first-line chemotherapy in patients with metastatic colorectal cancer: a multicenter retrospective study

Abstract

The addition of bevacizumab to standard chemotherapy has improved progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) in both first- and second line treatment, but the role of maintenance bevacizumab remains controversial. The association of various clinical factor and survival was examined in this retrospective cohort analysis. The clinical data from 220 previously untreated patients with mCRC, not progressive at the end of standard chemotherapy plus bevacizumab, were collected and analyzed. Patients were classified into two subgroups: those given with maintenance bevacizumab: "maintenance bevacizumab cohort (n = 118; MB)", and those discontinuing bevacizumab as a result of physician's or patient's decision: "no maintenance bevacizumab cohort (n = 102; noMB)". The baseline factors were well balanced between the study subgroups. Median PFS and OS for the general population was 10 months (range 7-15) and 22.5 months (range 18-26), respectively. Median PFS was 13 and 8 months in the BM and noBM cohorts, respectively (p < 0.0001). In the multivariate analysis, maintenance therapy resulted independently associated with improved PFS (HR 1.73; p < 0.001), but only objective response (OR) after first-line chemotherapy was associated with improved OS. Maintenance chemotherapy cannot be considered a standard of care after induction chemotherapy for mCRC, because the optimal balance between efficacy and safety of maintenance therapy remains a significant challenge. The results of our retrospective study suggest that maintenance therapy with bevacizumab is a safe and valuable option, particularly in those patients achieving an objective response after first-line chemotherapy.

Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

“…The only significant differences were in the subgroups BEVA versus no BBP [42, 73, 81, 83, 85] (MD = 4.89; 95% CI 1.91–7.87; I 2  = 73%), favoring BEVA (Table 3; Fig. 1).…”

“…OS and PFS had been assessed in all the intervention subgroups described, and PPS had been assessed in only one intervention subgroup (BEVA vs no BBP) [42, 73, 81, 84, 85]. …”

“…In the meta-analysis, we assessed eight studies that had described severe adverse events [72, 77, 83–85, 88, 89] for safety, including hypertension, arterial thromboembolism, venous thromboembolism, gastrointestinal perforation, bleeding, diarrhea, neutropenia, and other severe adverse events (Table 4). …”

Molecularly targeted drugs for metastatic colorectal cancer

“…In a Phase III trial to compare the efficacy and safety of bevacizumab alone with bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with mCRC, Díaz-Rubio et al did not find statistically significant differences in the median PFS or OS times between bevacizumab-treated versus XELOX plus bevacizumab-treated patients 41. The results of a recent retrospective study indicate that the maintenance therapy with bevacizumab is a safe and valuable option in mCRC patients, especially in those who achieve an objective response after first-line chemotherapy 42. In addition, two reports from the 2013 American Society of Clinical Oncology (ASCO) annual meeting support the use of bevacizumab in maintenance treatment of mCRC 43,44…”

Anti-angiogenic agents in metastatic colorectal cancer

“…The study results favored bevacizumab maintenance over no maintenance therapy (PFS: 13 mo vs 8 mo; P < 0.0001). An OS advantage was only seen in those patients who received bevacizumab maintenance after they had an objective response to induction chemotherapy [39] . More recently, the role of bevacizumab plus chemotherapy as maintenance therapy was investigated in the phase Ⅲ CAIRO3 trial.…”