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. 2020 May 16;12(5):1259.
doi: 10.3390/cancers12051259.

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  1   2 , Alessio Cortellini  2 , Katia Cannita  1 , Olga Venditti  1 , Floriana Camarda  3   4 , Maria Alessandra Calegari  3   4 , Lisa Salvatore  3   4 , Giampaolo Tortora  3   4 , Daniele Rossini  5   6 , Marco Maria Germani  5   6 , Alessandra Boccaccino  5   6 , Emanuela Dell'Aquila  7 , Claudia Fulgenzi  7 , Daniele Santini  7 , Michele De Tursi  8 , Nicola Tinari  8 , Pietro Di Marino  9 , Pasquale Lombardi  10 , Susana Roselló Keränen  11   12 , Marisol Huerta Álvaro  11 , Ina Valeria Zurlo  3   13 , Domenico Cristiano Corsi  13 , Alessandra Emiliani  13 , Nicoletta Zanaletti  14 , Teresa Troiani  14 , Pasquale Vitale  14 , Riccardo Giampieri  15 , Filippo Merloni  15 , Mario Alberto Occhipinti  16 , Paolo Marchetti  16   17 , Michela Roberto  17 , Federica Mazzuca  17 , Michele Ghidini  18 , Alice Indini  18 , Ingrid Garajova  19 , Federica Zoratto  20 , Simona Delle Monache  21 , Giampiero Porzio  1   2 , Corrado Ficorella  1   2
Affiliations

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 et al. Cancers (Basel). .

Abstract

: 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: Aflibercept; Bevacizumab; Cetuximab; Panitumumab; RAS wild-type mCRC; anti-angiogenics; second-line treatment.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Kaplan–Meyer PFS (A) and OS (B) curves according to the second-line regimen.
Figure 2
Figure 2
Incidence of G1/G2 (A) and G3/G4 (B) VEGF inhibitors class-specific adverse events according to the second-line regimen. AV: arteriovenous; GI: gastrointestinal.
See this image and copyright information in PMC

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