title: FOLFIRI-bevacizumab as first-line chemotherapy in 3500 patients with advanced colorectal cancer: a pooled analysis of 29 published trials.
abstract: Irinotecan and infusional bolus 5-fluorouracil (5-FU)-based chemotherapy (FOLFIRI [5-fluorouracil, folinic acid, irinotecan]) + bevacizumab (FOLFIRI-B) is 1 of the cornerstones of first-line treatment of advanced colorectal cancer (CRC). However, bevacizumab was approved for use after the AVF2107 trial that included a bolus 5-FU schedule (IFL [irinotecan + 5-FU + leucovorin]). No randomized trials have been published comparing FOLFIRI and FOLFIRI-B. The aim of this review is to pool all published data on the activity and efficacy of FOLFIRI-B as first-line therapy in treating advanced CRC in prospective and retrospective studies. We performed a systematic review, through PubMed and EMBASE, of all prospective and retrospective published studies exploring the efficacy of FOLFIRI-B as first-line chemotherapy in patients with advanced CRC. Pooled estimates of the response rate (RR) and weighted median of progression-free survival (PFS) and overall survival (OS) from all FOLFIRI-B-related studies were calculated. Rates of metastasectomy and bevacizumab-related severe toxicities were reported. A total of 29 studies (8 randomized controlled trials, 1 phase IV trial, 2 phase II trials, 4 observational studies, 4 prospective nonrandomized cohort studies, and 10 retrospective case series) were retrieved for a total of 3502 patients. Overall, the pooled RR (n = 22 publications) was 51.4%. Median PFS and OS (n = 25 and 20 publications) were 10.8 months (95% confidence interval [CI], 8.9-12.8) and 23.7 months (95% CI, 18.1-31.6), respectively. The pooled rate of surgical resection of metastases (any site of surgery: n = 7 publications) was 9.3% (range, 3.6%-24%), and rate of liver resections (liver surgery only: n = 7 publications) was 18% (range 8%-25%). Grade 3-4 bevacizumab-related toxicities were also comparable with larger phase III trials. FOLFIRI-B is used worldwide as upfront treatment for stage IV CRC. This indication is confirmed by robust data about RR, PFS, and survival obtained, which this pooled analysis of 29 trials also found. FOLFIRI-B remains 1 of the referent combinations when bevacizumab is considered as first-line therapy.
authors.affiliation: Medical Oncology Unit, Oncology Department, Azienda Ospedaliera Treviglio, Treviglio (BG), Italy. faupe@libero.it
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.forename: Karen
authors.initials: K
authors.lastname: Borgonovo
authors.forename: Mary
authors.initials: M
authors.lastname: Cabiddu
authors.forename: Mara
authors.initials: M
authors.lastname: Ghilardi
authors.forename: Veronica
authors.initials: V
authors.lastname: Lonati
authors.forename: Federica
authors.initials: F
authors.lastname: Maspero
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sauta
authors.forename: Giordano Domenico
authors.initials: GD
authors.lastname: Beretta
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Bevacizumab; Chemotherapy; Colorectal cancer; FOLFIRI; First line