title: Bevacizumab plus XELOX as first-line treatment of metastatic colorectal cancer: The OBELIX study.
abstract: OBJECTIVE
  To confirm the efficacy and safety of bevacizumab/XELOX combination for the treatment of locally advanced or metastatic colorectal cancer (CRC) in Italy.
  
  
  METHODS
  This multicentric, prospective, open-label study included patients with CRC previously untreated with chemotherapy. Patients were administered bevacizumab in combination with XELOX. The primary efficacy end-point was progression-free survival (PFS). Secondary end-points included time to overall response (TOR), duration of response (DOR), time to treatment failure (TTF) and overall survival (OS). The incidence and type of adverse events AEs and severe AEs were evaluated. Also, the mutational status of BRAF and KRAS was assessed by high resolution melting and direct sequencing, and quality of life (QoL) was measured by the EuroQoL EQ-5D questionnaire at baseline and at the last visit.
  
  
  RESULTS
  The intention-to-treat population included 197 patients (mean age: 62.3 ± 9.9 years, 56.4% males). At baseline, 16/34 evaluable subjects (47.1%) harbored a KRAS and/or a BRAF mutation; the mean QoL index was 80.2 ± 14.3. First-line therapy was given for 223.7 ± 175.9 d, and after a mean follow-up of 387.7 ± 238.8 d all patients discontinued from the study mainly for disease progression (PD, 45.4%) and AEs (25.4%). Median PFS was 9.7 mo (95%CI: 8.4-10.5) and the median values for secondary end-points were: TOR = 3.9 mo (95%CI: 2.6-4.7), DOR = 8.5 mo (95%CI: 7.3-10.3), TTF = 6.7 mo (95%CI: 6.0-7.7) and OS = 23.2 mo (95%CI: 20.1-27.2). Patients carrying at least one lesion had a lower overall response rate (66.7% vs 88.9%) and a lower probability of achieving complete or partial response than those without mutations, but the difference in relative risk was not statistically significant (P = 0.2). Mean EQ-5D-3L raw index score significantly decreased to 74.9 ± 19.1 at the last visit (signed-rank test, P = 0.0076), but in general the evaluation on QoL perceived by patients was good.
  
  
  CONCLUSIONS
  The efficacy of bevacizumab in combination with XELOX in terms of PFS in patients with aCRC or mCRC in Italy was confirmed, with acceptable toxicity.
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Antonuzzo
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giommoni
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Pastorelli
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Latiano
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Pavese
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Azzarello
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Aieta
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pastina
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Fabio
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolini
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Domenico Cristiano
authors.initials: DC
authors.lastname: Corsi
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Selene
authors.initials: S
authors.lastname: Mogavero
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Angelini
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Pazzagli
authors.affiliation: Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D057194:Intention to Treat Analysis; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010071:Oxaloacetates; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011788:Quality of Life; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; C117307:KRAS protein, human; D010071:Oxaloacetates; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D005472:Fluorouracil
keywords: Bevacizumab; Chemotherapy; Colorectal neoplasms; XELOX; anti-Vascular endothelial growth factor