Abstract: Background: Metastatic colorectal cancer (mCRC) patients who progress on oxaliplatin-based chemotherapy benefit from second-line treatment with FOLFIRI plus the antiangiogenic drug aflibercept. However, the absence of validated biomarkers for antiangiogenic therapies remains a challenge. In this context, we previously reported that combining plasma VEGF-A levels, a circulating microRNA profile, and patient clinical characteristics predicts outcomes in FOLFIRI plus aflibercept treatment. In the present study, we now report biomarkers of response to FOLFIRI plus aflibercept in elderly mCRC patients who progressed after first-line oxaliplatin-based chemotherapy. Methods: The study included 154 mCRC patients over 70 years of age enrolled in the clinical phase II trial AFEMA. Plasma samples were obtained before FOLFIRI plus aflibercept treatment, and circulating levels of VEGF-A and 13 miRNAs were analysed. Results: The levels of VEGF-A and five of these 13 miRNAs (miR-193-3b, miR-432-5p, miR-29c-3p, miR-93-5p, miR-30a-3p) enabled the stratification of patients based on progression-free survival and time-to-treatment failure. Specifically, combining miR-29c-3p with VEGF-A improved prognostic accuracy. Conclusion: Our study underscores the value of integrating miR-29c-3p analysis with VEGF-A as a biomarker strategy to advance the management of elderly
mCRC patients receiving FOLFIRI plus aflibercept, improving outcome predictions and enabling more personalised therapeutic strategies.
