PMID- 32429380
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 5
DP  - 2020 May 16
TI  - Evaluation of Second-line Anti-VEGF after First-line Anti-EGFR Based Therapy in 
      RAS Wild-Type Metastatic Colorectal Cancer: The Multicenter "SLAVE" Study.
LID - 10.3390/cancers12051259 [doi]
LID - 1259
AB  - : Background: The optimal anti-angiogenic strategy as second-line treatment in 
      RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR 
      (Epidermal Growth Factor Receptor) based first-line treatment is still debated. 
      METHODS: This multicenter, real-world, retrospective study is aimed at evaluating 
      the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments 
      after an anti-EGFR based first-line regimen. Clinical outcomes measured were: 
      objective response rate (ORR), progression free survival (PFS), overall survival 
      (OS) and adverse events (AEs) profiles. RESULTS: From February 2011 to October 
      2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or 
      Aflibercept-based (49, 17.7%) regimen. No significant difference was found 
      regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7-34.4). 
      Aflibercept-treated group had a significantly shorter PFS compared to 
      Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 
      0.95-1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and 
      Aflibercept-treated group was 16.2 (95%CI: 15.3-18.1) and 12.7 (95%CI: 8.8-17.5) 
      months, respectively (HR= 1.31 (95%CI: 0.89-1.93) p = 0.16). After adjusting for 
      the key covariates (age, gender, performance status, number of metastatic sites 
      and primary tumor side) Bevacizumab-based regimens revealed to be significantly 
      related with a prolonged PFS (HR = 1.44 (95%CI: 1.02-2.03); p = 0.0399) compared 
      to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 
      0.99-2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific 
      AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the 
      Aflibercept-treated group, respectively (p = 0.0001). CONCLUSION: Our analysis 
      seems to reveal that Bevacizumab-based regimens have a slightly better PFS and 
      class-specific AEs profile compared to Aflibercept-based regimen as second-line 
      treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based 
      treatments. These results have to be taken with caution and no conclusive 
      considerations are allowed.
FAU - Parisi, Alessandro
AU  - Parisi A
AD  - Medical Oncology, St. Salvatore Hospital, University of L'Aquila, 67100 L'Aquila, 
      Italy.
AD  - Department of Biotechnology and Applied Clinical Sciences, University of 
      L'Aquila, 67100 L'Aquila, Italy.
FAU - Cortellini, Alessio
AU  - Cortellini A
AD  - Department of Biotechnology and Applied Clinical Sciences, University of 
      L'Aquila, 67100 L'Aquila, Italy.
FAU - Cannita, Katia
AU  - Cannita K
AD  - Medical Oncology, St. Salvatore Hospital, University of L'Aquila, 67100 L'Aquila, 
      Italy.
FAU - Venditti, Olga
AU  - Venditti O
AD  - Medical Oncology, St. Salvatore Hospital, University of L'Aquila, 67100 L'Aquila, 
      Italy.
FAU - Camarda, Floriana
AU  - Camarda F
AD  - Universita Cattolica del Sacro Cuore, 00168 Roma, Italy.
AD  - IRCCS-Comprehensive Cancer Center, Policlinico Universitario Agostino Gemelli, 
      00168 Roma, Italy.
FAU - Calegari, Maria Alessandra
AU  - Calegari MA
AD  - Universita Cattolica del Sacro Cuore, 00168 Roma, Italy.
AD  - IRCCS-Comprehensive Cancer Center, Policlinico Universitario Agostino Gemelli, 
      00168 Roma, Italy.
FAU - Salvatore, Lisa
AU  - Salvatore L
AUID- ORCID: 0000-0003-3864-0719
AD  - Universita Cattolica del Sacro Cuore, 00168 Roma, Italy.
AD  - IRCCS-Comprehensive Cancer Center, Policlinico Universitario Agostino Gemelli, 
      00168 Roma, Italy.
FAU - Tortora, Giampaolo
AU  - Tortora G
AD  - Universita Cattolica del Sacro Cuore, 00168 Roma, Italy.
AD  - IRCCS-Comprehensive Cancer Center, Policlinico Universitario Agostino Gemelli, 
      00168 Roma, Italy.
FAU - Rossini, Daniele
AU  - Rossini D
AD  - Department of Oncology, University Hospital of Pisa, 56100 Pisa, Italy.
AD  - Department of Translational Research and New Technologies in Medicine, University 
      of Pisa, 56100 Pisa, Italy.
FAU - Germani, Marco Maria
AU  - Germani MM
AD  - Department of Oncology, University Hospital of Pisa, 56100 Pisa, Italy.
AD  - Department of Translational Research and New Technologies in Medicine, University 
      of Pisa, 56100 Pisa, Italy.
FAU - Boccaccino, Alessandra
AU  - Boccaccino A
AD  - Department of Oncology, University Hospital of Pisa, 56100 Pisa, Italy.
AD  - Department of Translational Research and New Technologies in Medicine, University 
      of Pisa, 56100 Pisa, Italy.
FAU - Dell'Aquila, Emanuela
AU  - Dell'Aquila E
AD  - Medical Oncology, Campus Bio-Medico, University of Rome, 00128 Rome, Italy.
FAU - Fulgenzi, Claudia
AU  - Fulgenzi C
AD  - Medical Oncology, Campus Bio-Medico, University of Rome, 00128 Rome, Italy.
FAU - Santini, Daniele
AU  - Santini D
AD  - Medical Oncology, Campus Bio-Medico, University of Rome, 00128 Rome, Italy.
FAU - Tursi, Michele De
AU  - Tursi M
AD  - Department of Medical, Oral and Biotechnological Sciences and Center for Advance 
      Studies and Technology (CAST), G. D'Annunzio University, 66100 Chieti, Italy.
FAU - Tinari, Nicola
AU  - Tinari N
AD  - Department of Medical, Oral and Biotechnological Sciences and Center for Advance 
      Studies and Technology (CAST), G. D'Annunzio University, 66100 Chieti, Italy.
FAU - Marino, Pietro Di
AU  - Marino PD
AD  - Clinical Oncology Unit, S.S. Annunziata Hospital, 66100 Chieti, Italy.
FAU - Lombardi, Pasquale
AU  - Lombardi P
AD  - Department of Oncology, University of Turin, Candiolo Cancer Institute-FPO-IRCCS, 
      10060 Candiolo,Italy;.
FAU - Keranen, Susana Rosello
AU  - Keranen SR
AD  - Department of Medical Oncology, INCLIVA Biomedical Research Institute, University 
      of Valencia, 46010 Valencia, Spain.
AD  - Instituto de Salud Carlos III, CIBERONC, 28220 Madrid, Spain.
FAU - Alvaro, Marisol Huerta
AU  - Alvaro MH
AD  - Department of Medical Oncology, INCLIVA Biomedical Research Institute, University 
      of Valencia, 46010 Valencia, Spain.
FAU - Zurlo, Ina Valeria
AU  - Zurlo IV
AD  - Universita Cattolica del Sacro Cuore, 00168 Roma, Italy.
AD  - UOC Oncologia Medica San Giovanni Calibita Fatebenefratelli Roma, 00186 
      Roma,Italy.
FAU - Corsi, Domenico Cristiano
AU  - Corsi DC
AD  - UOC Oncologia Medica San Giovanni Calibita Fatebenefratelli Roma, 00186 
      Roma,Italy.
FAU - Emiliani, Alessandra
AU  - Emiliani A
AD  - UOC Oncologia Medica San Giovanni Calibita Fatebenefratelli Roma, 00186 
      Roma,Italy.
FAU - Zanaletti, Nicoletta
AU  - Zanaletti N
AD  - Department of Precision Medicine, Universita della Campania "Luigi Vanvitelli", 
      80131 Napoli, Italy.
FAU - Troiani, Teresa
AU  - Troiani T
AD  - Department of Precision Medicine, Universita della Campania "Luigi Vanvitelli", 
      80131 Napoli, Italy.
FAU - Vitale, Pasquale
AU  - Vitale P
AD  - Department of Precision Medicine, Universita della Campania "Luigi Vanvitelli", 
      80131 Napoli, Italy.
FAU - Giampieri, Riccardo
AU  - Giampieri R
AD  - Clinica Oncologica e Centro Regionale di Genetica Oncologica, Universita 
      Politecnica delle Marche, AOU Ospedali Riuniti-Ancona, 60020 Ancona, Italy.
FAU - Merloni, Filippo
AU  - Merloni F
AD  - Clinica Oncologica e Centro Regionale di Genetica Oncologica, Universita 
      Politecnica delle Marche, AOU Ospedali Riuniti-Ancona, 60020 Ancona, Italy.
FAU - Occhipinti, Mario Alberto
AU  - Occhipinti MA
AD  - Medical Oncology, Policlinico Umberto I, 00161 Rome, Italy.
FAU - Marchetti, Paolo
AU  - Marchetti P
AD  - Medical Oncology, Policlinico Umberto I, 00161 Rome, Italy.
AD  - Department of Clinical and Molecular Medicine, Oncology Unit, Sant'Andrea 
      Hospital, Sapienza University of Rome, 00189 Rome, Italy.
FAU - Roberto, Michela
AU  - Roberto M
AD  - Department of Clinical and Molecular Medicine, Oncology Unit, Sant'Andrea 
      Hospital, Sapienza University of Rome, 00189 Rome, Italy.
FAU - Mazzuca, Federica
AU  - Mazzuca F
AD  - Department of Clinical and Molecular Medicine, Oncology Unit, Sant'Andrea 
      Hospital, Sapienza University of Rome, 00189 Rome, Italy.
FAU - Ghidini, Michele
AU  - Ghidini M
AD  - Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 
      20122 Milano, Italy.
FAU - Indini, Alice
AU  - Indini A
AD  - Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 
      20122 Milano, Italy.
FAU - Garajova, Ingrid
AU  - Garajova I
AD  - Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, 
      Italy.
FAU - Zoratto, Federica
AU  - Zoratto F
AD  - Medical Oncology, Santa Maria Goretti Hospital, 04100 Latina, Italy.
FAU - Monache, Simona Delle
AU  - Monache SD
AD  - Department of Biotechnological and Applied Clinical Sciences, Laboratory of 
      Applied Biology, University of L'Aquila, 67100 L'Aquila, Italy.
FAU - Porzio, Giampiero
AU  - Porzio G
AD  - Medical Oncology, St. Salvatore Hospital, University of L'Aquila, 67100 L'Aquila, 
      Italy.
AD  - Department of Biotechnology and Applied Clinical Sciences, University of 
      L'Aquila, 67100 L'Aquila, Italy.
FAU - Ficorella, Corrado
AU  - Ficorella C
AD  - Medical Oncology, St. Salvatore Hospital, University of L'Aquila, 67100 L'Aquila, 
      Italy.
AD  - Department of Biotechnology and Applied Clinical Sciences, University of 
      L'Aquila, 67100 L'Aquila, Italy.
LA  - eng
PT  - Journal Article
DEP - 20200516
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7281759
OTO - NOTNLM
OT  - Aflibercept
OT  - Bevacizumab
OT  - Cetuximab
OT  - Panitumumab
OT  - RAS wild-type mCRC
OT  - anti-angiogenics
OT  - second-line treatment
COIS- Alessio Cortellini received grants as a speaker by MSD and Astra-Zeneca, grant 
      consultancies by BMS, Roche, Novartis and Astellas. Dr. Daniele Rossini received 
      personal fees from Takeda. Dr. Ingrid Garajova received grants as a speaker by 
      Amgen and Takeda. The other authors declare no conflict of interest.
EDAT- 2020/05/21 06:00
MHDA- 2020/05/21 06:01
PMCR- 2020/05/16
CRDT- 2020/05/21 06:00
PHST- 2020/04/25 00:00 [received]
PHST- 2020/05/11 00:00 [revised]
PHST- 2020/05/14 00:00 [accepted]
PHST- 2020/05/21 06:00 [entrez]
PHST- 2020/05/21 06:00 [pubmed]
PHST- 2020/05/21 06:01 [medline]
PHST- 2020/05/16 00:00 [pmc-release]
AID - cancers12051259 [pii]
AID - cancers-12-01259 [pii]
AID - 10.3390/cancers12051259 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 May 16;12(5):1259. doi: 10.3390/cancers12051259.