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.

Evaluation of second-line anti-VEGF after first-line anti-EGFR based therapy in RAS wild-type metastatic colorectal cancer. The multicenter “SLAVE” study / Parisi, A.; Cortellini, A.; Cannita, K.; Venditti, O.; Camarda, F.; Calegari, M. A.; Salvatore, L.; Tortora, G.; Rossini, D.; Germani, M. M.; Boccaccino, A.; Dell'Aquila, E.; Fulgenzi, C.; Santini, D.; De Tursi, M.; Tinari, N.; Di Marino, P.; Lombardi, P.; Keranen, S. R.; Alvaro, M. H.; Zurlo, I. V.; Corsi, D. C.; Emiliani, A.; Zanaletti, N.; Troiani, T.; Vitale, P.; Giampieri, R.; Merloni, F.; Occhipinti, M.; Marchetti, P.; Roberto, M.; Mazzuca, F.; Ghidini, M.; Indini, A.; Garajova, I.; Zoratto, F.; Monache, S. D.; Porzio, G.; Ficorella, C.. - In: CANCERS. - ISSN 2072-6694. - 12:5(2020), pp. 1-14. [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

Santini D.;Occhipinti M.;Marchetti P.;Roberto M.;Mazzuca F.;Zoratto F.;
2020

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.
2020
aflibercept; anti-angiogenics; bevacizumab; cetuximab; panitumumab; ras wild-type mcrc; second-line treatment
01 Pubblicazione su rivista::01a Articolo in rivista
Evaluation of second-line anti-VEGF after first-line anti-EGFR based therapy in RAS wild-type metastatic colorectal cancer. The multicenter “SLAVE” study / Parisi, A.; Cortellini, A.; Cannita, K.; Venditti, O.; Camarda, F.; Calegari, M. A.; Salvatore, L.; Tortora, G.; Rossini, D.; Germani, M. M.; Boccaccino, A.; Dell'Aquila, E.; Fulgenzi, C.; Santini, D.; De Tursi, M.; Tinari, N.; Di Marino, P.; Lombardi, P.; Keranen, S. R.; Alvaro, M. H.; Zurlo, I. V.; Corsi, D. C.; Emiliani, A.; Zanaletti, N.; Troiani, T.; Vitale, P.; Giampieri, R.; Merloni, F.; Occhipinti, M.; Marchetti, P.; Roberto, M.; Mazzuca, F.; Ghidini, M.; Indini, A.; Garajova, I.; Zoratto, F.; Monache, S. D.; Porzio, G.; Ficorella, C.. - In: CANCERS. - ISSN 2072-6694. - 12:5(2020), pp. 1-14. [10.3390/cancers12051259]
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