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J Clin Oncol. 2018 Mar 10;36(8):773-779. doi: 10.1200/JCO.2017.76.9901. Epub 2018 Jan 20.

Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.

Author information

1
Michael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology Research, Ltd., Southport, Queensland, Australia; Heinz-Josef Lenz, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Michael A. Morse, Duke University Medical Center, Durham, NC; Eric Van Cutsem, University Hospitals Gasthuisberg Leuven and Katholieke Universiteit Leuven, Leuven; Alain Hendlisz, Institut Jules Bordet; Bart Neyns, Universitair Ziekenhuis Brussel, Brussels; Jean-Marie Ledeine, Bristol-Myers Squibb, Braine-L'Alleud, Belgium; Ray McDermott, St Vincent's University Hospital and Cancer Trials Ireland, Dublin, Ireland; Michael B. Sawyer, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada; Magali Svrcek and Thierry André, Hopital Saint Antoine, Assistance Publique Hôpitaux de Paris and Sorbonne Universités, Université Pierre et Marie Curie, Paris, France; and Rebecca A. Moss, Z. Alexander Cao, and Shital Kamble, Bristol-Myers Squibb, Princeton, NJ.

Abstract

Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02060188.

PMID:
29355075
DOI:
10.1200/JCO.2017.76.9901
[Indexed for MEDLINE]

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