Josep Tabernero1, Eric Van Cutsem2, Radek Lakomý3, Jana Prausová4, Paul Ruff5, Guy A van Hazel6, Vladimir M Moiseyenko7, David R Ferry8, Joseph J McKendrick9, Karen Soussan-Lazard10, Soazig Chevalier10, Carmen J Allegra11. 1. Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jtabernero@vhio.net. 2. University Hospitals Leuven and KU Leuven, Belgium. 3. Masaryk Memorial Cancer Institute, Brno, Czech Republic. 4. Fakultni nemocnice v Motole, Praha, Czech Republic. 5. University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa. 6. University of Western Australia, Western Australia, Australia. 7. Oncology Research Institute Na.NN.Petrov, St-Petersburg, Russian Federation. 8. Russells Hall Hospital, Dudley, West Midlands, UK. 9. Monash University, Victoria, Australia. 10. Sanofi, Vitry-sur-Seine, France. 11. University of Florida, Gainesville, United States.
Abstract
PURPOSE: The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. METHODS: Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status). RESULTS:Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined. CONCLUSIONS: The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated withoxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment.
RCT Entities:
PURPOSE: The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. METHODS:Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status). RESULTS: Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined. CONCLUSIONS: The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment.
Authors: Rachel P Riechelmann; Luiz S Leite; Giovanni M Bariani; Joao Glasberg; Thomas G Rivelli; Leonardo Gomes da Fonseca; Daniela R Nebuloni; Maria I Braghiroli; Marcelo A Queiroz; Alice M Isejima; Christian Kappeler; Luciana Kikuchi; Paulo M Hoff Journal: Oncologist Date: 2019-06-07
Authors: John L Nosher; Inaya Ahmed; Akshar N Patel; Vyacheslav Gendel; Philip G Murillo; Rebecca Moss; Salma K Jabbour Journal: J Gastrointest Oncol Date: 2015-04
Authors: Cathal O'Leary; Megan Greally; John McCaffrey; Peter Hughes; Leo L P Lawler; Martin O'Connell; Tony Geoghegan; Cormac Farrelly Journal: Ir J Med Sci Date: 2018-03-06 Impact factor: 1.568