Cancers (May 2020)

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 Álvaro,
  • Ina 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

DOI
https://doi.org/10.3390/cancers12051259
Journal volume & issue
Vol. 12, no. 5
p. 1259

Abstract

Read online

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.

Keywords