Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer

Michael J. Overman, Sara Lonardi, Ka Yeung Mark Wong, Heinz Josef Lenz, Fabio Gelsomino, Massimo Aglietta, Michael A. Morse, Eric Van Cutsem, Ray McDermott, Andrew Hill, Michael B. Sawyer, Alain Hendlisz, Bart Neyns, Magali Svrcek, Rebecca A. Moss, Jean Marie Ledeine, Z. Alexander Cao, Shital Kamble, Scott Kopetz, Thierry André

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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 patientreported 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.

Original languageEnglish
Pages (from-to)773-779
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number8
DOIs
Publication statusPublished - Mar 10 2018

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Overman, M. J., Lonardi, S., Wong, K. Y. M., Lenz, H. J., Gelsomino, F., Aglietta, M., Morse, M. A., Van Cutsem, E., McDermott, R., Hill, A., Sawyer, M. B., Hendlisz, A., Neyns, B., Svrcek, M., Moss, R. A., Ledeine, J. M., Cao, Z. A., Kamble, S., Kopetz, S., & André, T. (2018). Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. Journal of Clinical Oncology, 36(8), 773-779. https://doi.org/10.1200/JCO.2017.76.9901