Evaluation of second-line anti-VEGF after first-line anti-EGFR based therapy in RAS wild-type metastatic colorectal cancer: The multicenter “SLAVE” study

Alessandro Parisi, Alessio Cortellini, Katia Cannita, Olga Venditti, Floriana Camarda, Maria Alessandra Calegari, Lisa Salvatore, Giampaolo Tortora, Daniele Rossini, Marco Maria Germani, Alessandra Boccaccino, Emanuela Dell’aquila, Claudia Fulgenzi, Daniele Santini, Michele De Tursi, Nicola Tinari, Pietro Di Marino, Pasquale Lombardi, Susana Roselló Keränen, Marisol Huerta ÁlvaroIna Valeria Zurlo, Domenico Cristiano Corsi, Alessandra Emiliani, Nicoletta Zanaletti, Teresa Troiani, Pasquale Vitale, Riccardo Giampieri, Filippo Merloni, Mario Alberto Occhipinti, Paolo Marchetti, Michela Roberto, Federica Mazzuca, Michele Ghidini, Alice Indini, Ingrid Garajova, Federica Zoratto, Simona Delle Monache, Giampiero Porzio, Corrado Ficorella

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1259
Issue number5
Publication statusPublished - May 2020


  • Aflibercept
  • Anti-angiogenics
  • Bevacizumab
  • Cetuximab
  • Panitumumab
  • RAS wild-type mCRC
  • Second-line treatment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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