Abstract 342P
Background
The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy have been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival.
Methods
Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR.
Results
A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment.
Conclusions
In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.
Clinical trial identification
N.º EudraCT: 2016-001508-45.
Editorial acknowledgement
Legal entity responsible for the study
Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD).
Funding
Sanofi Aventis.
Disclosure
M.A. Gomez España: Financial Interests, Institutional, Other, Grants or contracts: Alianza mixta en red de Andalucía-Roche ; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Amgen, Merck, Roche, Sanofi, Servier, Bayer, Pierre Fabre. M.J. Safont Aguileria: Financial Interests, Personal, Other, Consulting fees: Merck, Amgen, Sanofi, Servier; Financial Interests, Personal, Speaker’s Bureau: Merck, Amgen, Sanofi, Servier, Pierre Fabre, BMS, MSD; Financial Interests, Personal, Expert Testimony: Merck, Amgen, Sanofi, Servier, Pierre Fabre; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Merck, Amgen ; Financial Interests, Personal, Advisory Board: Amgen. A. Ruiz-Casado: Financial Interests, Personal, Invited Speaker: Servier, Viatris, Abbott; Financial Interests, Personal, Advisory Board: Sanofi, Bayer. E. Aranda Aguilar: Financial Interests, Personal, Advisory Role: Amgen, Bayer, BMS, Merck, Roche, Sanofi. All other authors have declared no conflicts of interest.