title: Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest.
abstract: Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors. We performed a pooled analysis of patients with unresectable and liver-limited mCRC, treated with first-line FOLFOXIRI plus bevacizumab in three prospective clinical trials by Gruppo Oncologico del Nord Ovest. 205 (37.9%) patients with liver-limited disease were selected, out of 541 treated patients. Liver metastases were synchronous, ≥4 and bilobar in 90%, 61%, and 79% of cases, respectively. The largest diameter was >5 cm in 42% of cases, and ≥6 segments were involved in 25%. Seventy-four patients (36.1%) underwent R0 or R1 resection of metastases. R2 resections were performed in 17 cases (8.3%). Having <6 involved segments (p < 0.001) and achieving RECIST response (p = 0.019) were associated with higher chances of resection. R0/R1 resected patients had significantly longer median progression-free survival (PFS) (18.1 versus 10.7 months, HR: 0.48 [0.35-0.66], p < 0.001) and overall survival (OS) (44.3 versus 24.4 months, HR: 0.32 [0.22-0.48], p < 0.001) compared with other patients, both in the univariate and multivariate analyses (PFS p = 0.025; OS p < 0.001). The 5-year PFS and OS rate in R0 resected patients were 12% and 43%, respectively. Neither negative baseline characteristics nor high clinical risk scores or RAS/BRAF mutations were associated with poor post-resection outcomes. In conclusion, FOLFOXIRI plus bevacizumab demonstrates efficacy in the conversion setting with considerable long-term outcome results independent of clinical and molecular prognostic factors (NCT00719797, NCT01163396 and NCT02271464).
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy; University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cremolini
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia, 15, 33010 Udine, Italy.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Casagrande
authors.affiliation: Unit of Medical Oncology 1, Istituto Oncologico Veneto, IRCSS, Via Gattamelata 64, 35128 Padua, Italy.
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia, 15, 33010 Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Unit of Medical Oncology 1, Istituto Oncologico Veneto, IRCSS, Via Gattamelata 64, 35128 Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bergamo
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy; University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy; University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Moretto R
authors.affiliation: Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy; University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marmorino
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy; University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Zucchelli
authors.affiliation: Division of Medicine and Medical Oncology, Azienda Istituti Ospitalieri, Viale Concordia 1, 26100 Cremona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
authors.affiliation: Department of Medical Oncology, University Campus Biomedico, Via Álvaro del Portillo 200, 00128 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Unit of Medical Oncology, "Felice Lotti" Hospital, Via Roma 147, 56025 Pontedera, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Allegrini
authors.affiliation: Unit of Medical Oncology, Azienda Sanitaria Ospedaliera Santa Croce e Carle, Via M. Coppino 26, 12100 Cuneo, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Granetto
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia, 15, 33010 Udine, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ferrari
authors.affiliation: Unit of Colorectal Surgery, Azienda Ospedaliero-Universitaria Pisana, Via Paradisa 2, 56125 Pisa, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Urbani
authors.affiliation: UOC Chirurgia Epatobiliare e Trapianto Epatico, Istituto Oncologico Veneto, IRCSS, via Giustiniani 2, 35128 Padua, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
authors.affiliation: Unit of General Surgery, "Sant'Antonio" Hospital ULSS16, via Facciolati 71, 35128 Padua, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Pilati
authors.affiliation: Pathology and Molecular Biology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sensi
authors.affiliation: Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Pellegrinelli
authors.affiliation: Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.affiliation: Pathology and Molecular Biology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy; University of Pisa, Via Roma 67, 56126 Pisa, Italy. Electronic address: alfredo.falcone@med.unipi.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Bevacizumab; FOLFOXIRI; Liver metastases; Metastatic colorectal cancer