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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Bevacizumab plus XELOX as first-line treatment of metastatic colorectal cancer: The OBELIX study
Lorenzo Antonuzzo, Elisa Giommoni, Davide Pastorelli, Tiziana Latiano, Ida Pavese, Domenico Azzarello, Michele Aieta, Ilaria Pastina, Francesca Di Fabio, Alessandro Bertolini, Domenico Cristiano Corsi, Selene Mogavero, Valentina Angelini, Mario Pazzagli, Francesco Di Costanzo
Lorenzo Antonuzzo, Elisa Giommoni, Francesco Di Costanzo, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy
Davide Pastorelli, Oncology of Rare Tumors, IRCCS, Istituto Oncologico Veneto, 35128 Padua, Italy
Tiziana Latiano, Medical Oncology, IRCCS, Casa Sollievo della Sofferenza, 71013 S. Giovanni Rotondo, Italy
Ida Pavese, Medical Oncology, Ospedale San Pietro Fatebenefratelli, 00189 Rome, Italy
Domenico Azzarello, Medical Oncology, Ospedale Bianchi Melacrino Morelli, 89125 Reggio Calabria, Italy
Michele Aieta, Medical Oncology, IRCCS CROB, 85028 Rionero, Italy
Ilaria Pastina, Medical Oncology, Ospedale della Misericordia, 58010 Grosseto, Italy
Alessandro Bertolini, Medical Oncology, Azienda Ospedaliera della Valtellina e della Valchiavenna, 23010 Sondrio, Italy
Domenico Cristiano Corsi, Medical Oncology, Ospedale San Giovanni Calibita Fatebenefratelli, 00186 Rome, Italy
Selene Mogavero, Primula Multimedia S.r.L, 56121 Pisa, Italy
Valentina Angelini, Roche S.p.A., 20811 Monza, Italy
Mario Pazzagli, Department of Experimental and Clinical Biomedical Sciences, Azienda Ospedaliero-Universitaria Careggi, 50139 Florence, Italy
Francesca Di Fabio, Medical Oncology, Policlinico S. Orsola-Malpighi, 40121 Bologna, Italy
Author contributions: Di Costanzo F, Antonuzzo L and Giommoni E were involved in trial design, patient recruitment, data analysis and in editing the manuscript; Pastorelli D, Latiano T, Pavese I, Azzarello D, Aieta M, Pastina I, Di Fabio F, Bertolini A, Corsi DC were involved in patient recruitment; Mogavero S and Angelini V were involved in editing the manuscript; Pazzagli M performed molecular biology analysis for KRAS and BRAF.
Ethics approval: this study was approved by the Independent Ethics Committee of each site.
Clinical trial registration: this study is registered at ClinicalTrials.gov. The registration identification number is NCT00577031.
Informed consent: all patients enrolled in the OBELIX trial provided informed written consent prior to study enrollment according to local ethical laws.
Conflict-of-interest: All authors have declared no conflicts of interest.
Data sharing: Regarding this study, technical appendix, statistical code and dataset are available from the corresponding author at (lorenzo.antonuzzo@gmail.com). Consent was not obtained by participants but the presented data are anonymized and risk of identification is low. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lorenzo Antonuzzo, MD, Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Viale Pieraccini 17, 50139 Firenze, Italy.
lorenzo.antonuzzo@gmail.com
Telephone: + 39-55-7947251 Fax: +39-55-7947538
Received: January 6, 2015
Peer-review started: January 7, 2015
First decision: February 10, 2015
Revised: March 13, 2015
Accepted: April 17, 2015
Article in press: April 17, 2015
Published online: June 21, 2015
Processing time: 164 Days and 21.8 Hours
AIM: 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.
CONCLUSION: 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.
Core tip: combined with fluorouracil-based chemotherapy, bevacizumab significantly improved survival, compared to placebo, in previously untreated metastatic colorectal cancer (mCRC) patients and in second-line treatment. In this perspective, the aim of this multicentric, prospective, open-label, single arm, non comparative study (the OBELIX study) was to confirm previous results on the positive outcome of bevacizumab/XELOX treatment in locally advanced CRC (aCRC) or mCRC patients in Italy. Our findings confirm the clinical benefit provided by bevacizumab plus XELOX in terms of proliferation-free survival, without the appearance of new areas of toxicity and an overall acceptable safety profile.
