MINOAS: A Single-arm Translational Phase II Trial of FOLFIRI Plus Aflibercept as First-line Therapy in Unresectable, Metastatic Colorectal Cancer.

Background: FOLFIRI/aflibercept is approved as a second-line treatment in metastatic colorectal cancer (mCRC) but there are limited data for its use as a first-line treatment.

Objective: To investigate the activity and safety of first-line FOLFIRI/aflibercept in mCRC, as well as to prospectively evaluate biomarkers of early response to treatment.

Patients And Methods: MINOAS was a phase II trial that aimed to evaluate the activity and toxicity of first-line FOLFIRI/aflibercept in mCRC. The primary endpoint was objective response rate (ORR). The secondary endpoints were toxicity, progression-free survival (PFS), overall survival (OS), and the evaluation of CEACAM-positive circulating tumor cells (CTC) and diffusion-weighted (DW)-MRI as biomarkers.

Results: Thirty-one patients were enrolled and 259 chemotherapy cycles were administered. At the time of the preplanned interim analysis, all patients had discontinued treatment and the ORR was 61.3%, crossing the activity threshold for trial discontinuation. Median PFS was 8.4 months (95% CI 7.8-9.0). Median OS had not been reached. There was one toxic death due to sepsis; grade 3/4 adverse events included neutropenia (n = 5), diarrhea (n = 6), hypertension (n = 4), asthenia (n = 3), proteinuria (n = 1), and bowel perforation (n = 1). Retaining CTC-negative status predicted better OS compared to continuous detection of CTCs (p = 0.015). Early decrease of the apparent diffusion coefficient (ADC) in DW-MRI was associated with an objective response.

Conclusion: The activity and safety of first-line FOLFIRI/aflibercept merit further evaluation in randomized studies. CLINICALTRIALS.

Gov Registration Number: NCT02624726.