Alessandro Parisi1, Giampiero Porzio2, Katia Cannita3, Olga Venditti3, Antonio Avallone4, Roberto Filippi5, Lisa Salvatore6, Giampaolo Tortora6, Marta Ribelli6, Olga Nigro7, Fabio Gelsomino8, Andrea Spallanzani8, Valeria Zurlo9, Silvana Leo9, Emanuela Dell'Aquila10, Fulgenzi Claudia10, Pasquale Lombardi11, Susana Roselló Keränen12, Giacomo Aimar13, Ilaria Depetris14, Riccardo Giampieri15, Cristina Morelli16, Michele De Tursi17, Nicola Tinari17, Francesca Romana Di Pietro18, Federica De Galitiis18, Nicoletta Zanaletti4, Teresa Troiani19, Pasquale Vitale19, Ingrid Garajova20, Michele Ghidini21, Gian Paolo Spinelli22, Federica Zoratto23, Michela Roberto24, Debora Ierino24, Angelica Petrillo25, Carla D'Orazio2, Corrado Ficorella2, Alessio Cortellini26. 1. Medical Oncology, St. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy. Electronic address: alexparis@hotmail.it. 2. Medical Oncology, St. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. 3. Medical Oncology, St. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy. 4. Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G.Pascale, Napoli, Italy. 5. Department of Oncology, University of Turin, Italy; Medical Oncology 1, Città della Salute e della Scienza di Torino, Italy. 6. Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy. 7. Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy. 8. Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, Modena, Italy. 9. Medical Oncology, "Vito Fazzi" Hospital, Lecce, Italy. 10. Medical Oncology, Campus Bio-Medico, University of Rome, Rome, Italy. 11. Department of Oncology, University of Turin, Italy. 12. Department of Medical Oncology. Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. 13. Department of Oncology, University of Turin, Italy; Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo (TO), Italy. 14. Medical Oncology, ASL TO4, Ospedale Civile di Ivrea, Ivrea, Turin, Italy. 15. Clinica Oncologica e Centro Regionale di Genetica Oncologica, Università Politecnica delle Marche, AOU Ospedali Riuniti-Ancona, Italy. 16. Medical Oncology Unit and PhD program in Systems and Experimental Medicine (XXXV cycle), Tor Vergata University Hospital, Rome, Italy. 17. Department of Medical, Oral and Biotechnological Sciences, Center for Advance Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy; Clinical Oncology Unit, S.S. Annunziata Hospital, Chieti, Italy. 18. IRCCS Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy. 19. Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", Napoli, Italy. 20. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 21. Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano. 22. UOC Territorial Oncology - AUSL Latina-CdS Aprilia, University of Rome "Sapienza", Italy. 23. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy. 24. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant'Andrea Hospital, Rome, Italy. 25. Medical Oncology Unit, Ospedale del Mare, Naples, Italy. 26. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
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.
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.
Authors: Alessandro Parisi; Riccardo Giampieri; Alex Mammarella; Cristiano Felicetti; Lisa Salvatore; Maria Bensi; Maria Grazia Maratta; Antonia Strippoli; Roberto Filippi; Maria Antonietta Satolli; Angelica Petrillo; Bruno Daniele; Michele De Tursi; Pietro Di Marino; Guido Giordano; Matteo Landriscina; Pasquale Vitale; Ina Valeria Zurlo; Emanuela Dell'Aquila; Silverio Tomao; Ilaria Depetris; Francesca Romana Di Pietro; Federica Zoratto; Davide Ciardiello; Maria Vittoria Pensieri; Ornella Garrone; Barbara Galassi; Claudio Ferri; Rossana Berardi; Michele Ghidini Journal: Front Oncol Date: 2022-08-12 Impact factor: 5.738