Clinicians’ Attitude to Doublet Plus Anti-EGFR Versus Triplet Plus Bevacizumab as First-line Treatment in Left-Sided RAS and BRAF Wild-Type Metastatic Colorectal Cancer Patients: A Multicenter, “Real-Life”, Case-Control Study

Alessandro Parisi, Giampiero Porzio, Katia Cannita, Olga Venditti, Antonio Avallone, Roberto Filippi, Lisa Salvatore, Giampaolo Tortora, Marta Ribelli, Olga Nigro, Fabio Gelsomino, Andrea Spallanzani, Valeria Zurlo, Silvana Leo, Emanuela Dell'Aquila, Fulgenzi Claudia, Pasquale Lombardi, Susana Roselló Keränen, Giacomo Aimar, Ilaria DepetrisRiccardo Giampieri, Cristina Morelli, Michele De Tursi, Nicola Tinari, Francesca Romana Di Pietro, Federica De Galitiis, Nicoletta Zanaletti, Teresa Troiani, Pasquale Vitale, Ingrid Garajova, Michele Ghidini, Gian Paolo Spinelli, Federica Zoratto, Michela Roberto, Debora Ierino, Angelica Petrillo, Carla D'Orazio, Corrado Ficorella, Alessio Cortellini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Doublets plus antiepidermal growth factor receptors monoclonal antibodies (EGFRi) are widely considered the preferable first-line regimen in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC), resulting superior in terms of activity and efficacy compared to doublets plus bevacizumab. However, data comparing doublet plus EGFRi and triplet plus bevacizumab are lacking, and the relative benefit of an intensive regimen plus an antiangiogenic backbone in this population is debated. Methods: This multicenter, retrospective study aimed at evaluating clinicians’ attitude to triplet-bevacizumab and doublet-EGFRi as first-line regimen in patients with left-sided RAS/BRAF wild-type mCRC treated in clinical practice at 22 Oncology Units from March 2012 to October 2020. A random case-control matching was performed to compare activity (ORR), and effectiveness (PFS, OS, secondary resection rate of metastases with curative intent) between triplet-bevacizumab and doublet-EGFRi, on the basis of ECOG-PS, age, gender, and burden of disease. Results: A total of 718 patients were consecutively treated with doublet-EGFRi (686, 95.5%) or triplet-bevacizumab (32, 4.5%). After case-control matching, median PFS was 13.6 (95% CI, 8.9-31.7) and 16.1 (95% CI, 12.1-36.8) months (P= .621), while median OS was 30.2 (95% CI, 14.4-69.5) and 38.1 (95% CI, 33.1-101.1) months (P= .0283) in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. The ORR was 65.6% and 90.6% (P= .016), while the secondary resection rate was 18.8% and 46.9% (P= .016), in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. Triplet-bevacizumab was associated with a higher incidence of G3/G4 neutropenia (25.0% vs. 12.5%, P= .041). Conclusion: Although a doublet-EGFRi remains the recommended upfront regimen in patients with left-sided RAS and BRAF wild-type mCRC, our real life data suggest a triplet-bevacizumab might be at least equally active and effective in properly selected cases.

Original languageEnglish
JournalClinical Colorectal Cancer
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Cetuximab
  • FOLFIRI
  • FOLFOX
  • FOLFOXIRI
  • mCRC
  • Panitumumab

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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