FOLFIRI + bevacizumab as second-line therapy for metastatic colorectal cancer pretreated with oxaliplatin: a pooled analysis of published trials

Abstract

Irinotecan and infusional 5-fluorouracil-based chemotherapy (FOLFIRI) plus bevacizumab (FOLFIRI-B) is one of the most effective treatments of advanced colorectal cancer (CRC). However, this schedule is regarded more extensively as first-line therapy and its efficacy has not been proven in phase III randomised trials in oxaliplatin-pretreated patients. We have performed a systematic review through PubMed and EMBASE, including all prospective and retrospective publications exploring the efficacy of FOLFIRI-B as second-line chemotherapy in advanced CRC patients pretreated with oxaliplatin and not with B. Pooled estimates of the response rates (RR), weighted medians of progression-free survival (PFS), and overall survival (OS) from all FOLFIRI-B-containing arms were calculated. A total of 11 studies (one randomised phase II trial, two phase II trials, two observational studies, two prospective non-randomised collections, and four retrospective case series) were retrieved giving a total of 435 patients. Overall, the pooled RR (n = 11 publications) was 26 %. Median PFS and OS (n = 11 and 10 publications, respectively) were 8.3 and 17.2 months. FOLFIRI-B is a reasonable and effective option for stage IV CRC pretreated with oxaliplatin and not exposed to B during first-line treatment. Its activity seems better than historical FOLFIRI-based second-line trials.

Use of Bevacizumab in the Management of Potentially Resectable Colorectal Liver Metastases: Safety, Pathologic Assessment and Benefit

“…A recent large pooled analysis including 29 studies confirmed the indication in this setting [12]. This same association was found active also in pre-treated patients, as shown in another report pooling data from 11 studies [13]. Likewise, an oxaliplatin-based regimen was initially found to be more active when combined to bevacizumab [7]; subsequent pooled analysis confirmed this finding, too [14].…”

Sequential administration of XELOX and XELIRI is effective, feasible and well tolerated by patients with metastatic colorectal cancer

“…According to a systematic review (Phase II) bevacizumab in combination with FOLFIRI prolongs the median PFS to 8.3 months compared with FOLFIRI alone, in the second-line setting (15). XELIRI in combination with bevacizumab was associated with a median PFS of 8.3 months in the second-line setting in the BIX study (6), which is considerably longer than in the present study, where the median PFS was 4.6 months (where 49% of patients were treated with bevacizumab).…”

Thromboembolic Disease in Advanced Colorectal Cancer Treated with Chemotherapy and Bevacizumab: A Case of Real “Pan-Thrombosis”

“…In this patient, bevacizumab was not started with the first-line FOLFOX regimen because the results of the NO16966 randomized phase III trial clearly showed that the addition of bevacizumab to FOLFOX was not associated with improved progression-free survival (HR 0.89, 97.5% CI 0.73-1.08), overall survival (OS) (HR 0.94, 95% CI 0.75-1.16), or overall response rate (38% in both arms) (6). The combination of FOLFIRI with bevacizumab (FOLFIRI-B) as second-line therapy for patients with metastatic CRC pretreated with oxaliplatin but not with bevacizumab was recently reviewed in a pooled analysis of retrospective and prospective trials involving 435 patients (7). The main conclusion was that FOLFIRI-B is a reasonable option for these patients.…”