학술논문
Aflibercept or bevacizumab in combination with FOLFIRI as second-line treatment of mRAS metastatic colorectal cancer patients: the ARBITRATION study protocol.
Document Type
Academic Journal
Author
Ottaiano A; Innovative Therapies for Abdominal Metastases Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', via M. Semmola, Naples, Campania 80131, Italy.; Scala S; Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Santorsola M; Innovative Therapies for Abdominal Metastases Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Trotta AM; Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; D'Alterio C; Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Portella L; Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Clemente O; Department of Abdominal Oncology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Nappi A; Department of Abdominal Oncology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Zanaletti N; Department of Abdominal Oncology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; De Stefano A; Department of Abdominal Oncology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Avallone A; Department of Abdominal Oncology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Granata V; Department of Radiology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Notariello C; Department of Abdominal Oncology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Luce A; Department of Precision Medicine, University of Campania 'L. Vanvitelli', Naples, Italy Biogem Scarl, Institute of Genetic Research, Laboratory of Precision and Molecular Oncology, Ariano Irpino, Italy.; Lombardi A; Department of Precision Medicine, University of Campania 'L. Vanvitelli', Naples, Italy Biogem Scarl, Institute of Genetic Research, Laboratory of Precision and Molecular Oncology, Ariano Irpino, Italy.; Picone C; Department of Radiology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Petrillo A; Department of Radiology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Perri F; Head and Neck Cancer Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Tatangelo F; Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Di Mauro A; Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Albino V; Hepatobiliary Surgical Oncology Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Izzo F; Hepatobiliary Surgical Oncology Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Rega D; Colorectal Cancer Surgery Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Pace U; Colorectal Cancer Surgery Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Di Marzo M; Colorectal Cancer Surgery Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Chiodini P; Medical Statistics Unit, University of Campania, Luigi Vanvitelli, Naples, Italy.; De Feo G; Scientific Directorate, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Del Prete P; Scientific Directorate, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Botti G; Scientific Directorate, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Delrio P; Colorectal Cancer Surgery Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.; Caraglia M; Department of Precision Medicine, University of Campania 'L. Vanvitelli', Naples, Italy Biogem Scarl, Institute of Genetic Research, Laboratory of Precision and Molecular Oncology, Ariano Irpino, Italy.; Nasti G; Innovative Therapies for Abdominal Metastases Unit, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.
Source
Publisher: Sage Country of Publication: England NLM ID: 101510808 Publication Model: eCollection Cited Medium: Print ISSN: 1758-8340 (Print) Linking ISSN: 17588340 NLM ISO Abbreviation: Ther Adv Med Oncol Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1758-8340
Abstract
Background: The intensive study of predictive factors has strongly ameliorated the therapeutic flow-chart of metastatic colorectal cancer (mCRC) by allowing the selection of patients who benefit from specific therapies. For instance, in mRAS (mutated RAS) mCRC patients, anti-EGFR drugs (cetuximab and panitumumab) are not recommended; in this group of patients, the use of anti-angiogenic drugs (bevacizumab and aflibercept) is predominant. However, at progression to standard bevacizumab-based first-line chemotherapy, still to date, there are no studies to guide oncologists in the choice of the best second-line anti-angiogenic drug (bevacizumab beyond progression versus aflibercept).
Methods: ARBITRATION is a prospective, observational study assessing efficacy differences between second-line fluorouracil/irinotecan (FOLFIRI)/bevacizumab versus FOLFIRI/aflibercept at progression to fluoropyrimidines, oxaliplatin and bevacizumab in mRAS mCRC patients. A test power of 80%, a median survival of 9 months from second-line treatment start and a hazard ratio of 0.67 between the two schedules were the basis for statistical design. The final sample will be 220 patients (110 per treatment). The significance will be verified with a two-tailed log-rank test with an alpha value of the I-type error of 5%. Time-to-outcome will be described by Kaplan-Meier curves and prognostic factors studied through multivariable analyses based on the Cox model. Secondary objectives include safety, responses' duration and progression-free survival. A translational research will be conducted to measure several angiogenic proteins in patients' serum before starting the therapy in order to evidence any angiogenic factor patterns related to outcome.
Discussion: We present a large, prospective, observational study aiming to answer two scientific questions: (1) outcome differences between second-line treatments with FOLFIRI/bevacizumab beyond progression versus FOLFIRI/aflibercept in mRAS mCRC patients, (2) angiogenic factors' patterns that could associate with efficacy and help oncologists to apply best the therapeutic anti-angiogenic strategies.
Trial Registration: The ARBITRATION trial (version 0.0, 13 April 2020) has been registered into the clinicaltrials.gov registry on 20 May 2020 with identifier NCT04397601.
Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.
(© The Author(s), 2021.)
Methods: ARBITRATION is a prospective, observational study assessing efficacy differences between second-line fluorouracil/irinotecan (FOLFIRI)/bevacizumab versus FOLFIRI/aflibercept at progression to fluoropyrimidines, oxaliplatin and bevacizumab in mRAS mCRC patients. A test power of 80%, a median survival of 9 months from second-line treatment start and a hazard ratio of 0.67 between the two schedules were the basis for statistical design. The final sample will be 220 patients (110 per treatment). The significance will be verified with a two-tailed log-rank test with an alpha value of the I-type error of 5%. Time-to-outcome will be described by Kaplan-Meier curves and prognostic factors studied through multivariable analyses based on the Cox model. Secondary objectives include safety, responses' duration and progression-free survival. A translational research will be conducted to measure several angiogenic proteins in patients' serum before starting the therapy in order to evidence any angiogenic factor patterns related to outcome.
Discussion: We present a large, prospective, observational study aiming to answer two scientific questions: (1) outcome differences between second-line treatments with FOLFIRI/bevacizumab beyond progression versus FOLFIRI/aflibercept in mRAS mCRC patients, (2) angiogenic factors' patterns that could associate with efficacy and help oncologists to apply best the therapeutic anti-angiogenic strategies.
Trial Registration: The ARBITRATION trial (version 0.0, 13 April 2020) has been registered into the clinicaltrials.gov registry on 20 May 2020 with identifier NCT04397601.
Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.
(© The Author(s), 2021.)