Therapeutic Advances in Medical Oncology (Mar 2021)

Aflibercept or bevacizumab in combination with FOLFIRI as second-line treatment of mRAS metastatic colorectal cancer patients: the ARBITRATION study protocol

  • Alessandro Ottaiano,
  • Stefania Scala,
  • Mariachiara Santorsola,
  • Anna Maria Trotta,
  • Crescenzo D’Alterio,
  • Luigi Portella,
  • Ottavia Clemente,
  • Anna Nappi,
  • Nicoletta Zanaletti,
  • Alfonso De Stefano,
  • Antonio Avallone,
  • Vincenza Granata,
  • Carmen Notariello,
  • Amalia Luce,
  • Angela Lombardi,
  • Carmine Picone,
  • Antonella Petrillo,
  • Francesco Perri,
  • Fabiana Tatangelo,
  • Annabella Di Mauro,
  • Vittorio Albino,
  • Francesco Izzo,
  • Daniela Rega,
  • Ugo Pace,
  • Massimiliano Di Marzo,
  • Paolo Chiodini,
  • Gianfranco De Feo,
  • Paola Del Prete,
  • Gerardo Botti,
  • Paolo Delrio,
  • Michele Caraglia,
  • Guglielmo Nasti

DOI
https://doi.org/10.1177/1758835921989223
Journal volume & issue
Vol. 13

Abstract

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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.