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

• Published in: Journal of clinical oncology Vol. 36; no. 8; pp. 773 - 779
• Main Authors: Overman, Michael J, Lonardi, Sara, Wong, Ka Yeung Mark, Lenz, Heinz-Josef, Gelsomino, Fabio, Aglietta, Massimo, Morse, Michael A, Van Cutsem, Eric, McDermott, Ray, Hill, Andrew, Sawyer, Michael B, Hendlisz, Alain, Neyns, Bart, Svrcek, Magali, Moss, Rebecca A, Ledeine, Jean-Marie, Cao, Z Alexander, Kamble, Shital, Kopetz, Scott, André, Thierry
• Format: Journal Article
• Language: English
• Published: United States 10-03-2018
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; DNA Mismatch Repair; Female; Humans; Ipilimumab - pharmacology; Ipilimumab - therapeutic use; Male; Microsatellite Instability; Middle Aged; Neoplasm Metastasis; Nivolumab - pharmacology; Nivolumab - therapeutic use; Survival Rate
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.76.9901

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.