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

Abstract

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.

• Authors: Alexios Matikas, John Souglakos, Panagiotis Katsaounis, Athanasios Kotsakis, Panagiotis Kouroupakis, Nikolaos Pantazopoulos, Nikolaos Kentepozidis, Adamantia Nikolaidi, Ippokratis Messaritakis, Ioanna Tzovara, Dora Hatzidaki, Efthymis Prinarakis, Vassilis Georgoulias
• Journal: Targeted oncology (Target Oncol) Vol. 14 Issue 3 Pg. 285-293 (06 2019) ISSN: 1776-260X [Electronic] France
• PMID: 31203498 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• aflibercept
• Irinotecan
• Receptors, Vascular Endothelial Growth Factor
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Colorectal Neoplasms (drug therapy, pathology)
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Humans
• Irinotecan (administration & dosage)
• Leucovorin (administration & dosage)
• Liver Neoplasms (drug therapy, secondary)
• Male
• Middle Aged
• Prognosis
• Receptors, Vascular Endothelial Growth Factor (administration & dosage)
• Recombinant Fusion Proteins (administration & dosage)
• Survival Rate