RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study

Romain Cohen,Yves Menu,David Tougeron,Aurélia Meurisse,Marie-Line Garcia-Larnicol,Thibault Mazard,Magali Svrcek,Dewi Vernerey,Christophe Tournigand,Jaafar Bennouna,Christophe Borg,Thierry André,Christelle De La Fouchardière,Benoist Chibaudel

doi:10.1136/jitc-2020-001499

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria may underestimate response...

Highlights

Microsatellite instability (MSI) is caused by the deficiency of the DNA mismatch repair (MMR) system, resulting from a germline mutation in MMR genes (Lynch syndrome) or from an epigenetic extinction of MLH1 gene.[1]
In this open-label, multicenter, phase II study, the combination of nivolumab and ipilimumab was associated with a low frequency of pseudoprogression and high clinical activity in patients with MSI/dMMR metastatic colorectal cancer (mCRC)
This is the first report of the pseudoprogression incidence in a large group of patients with mCRC with MSI/ dMMR tumors

Summary

Introduction

Microsatellite instability (MSI) is caused by the deficiency of the DNA mismatch repair (MMR) system, resulting from a germline mutation in MMR genes (Lynch syndrome) or from an epigenetic extinction of MLH1 gene (sporadic cases).[1]. Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability/ mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC). The GERCOR NIPICOL phase II study aimed to evaluate the frequency of pseudoprogressions in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab. Methods Patients with MSI/dMMR mCRC previously treated with fluoropyrimidines, oxaliplatin, and irinotecan with/without targeted therapies received nivolumab 3 mg/ kg plus ipilimumab 1 mg/kg every 3 weeks for four cycles nivolumab 3 mg/kg every 2 weeks until progression or a maximum of 20 cycles. The disease control rate (DCR) at 12 weeks was 86.0% with RECIST 1.1% and 87.7% with iRECIST. Conclusion Pseudoprogression is rare in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab. This combined ICI therapy confirms impressive DCR and survival outcomes in these patients.

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Results

Conclusion