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

Publication ,  Journal Article
Overman, MJ; Lonardi, S; Wong, KYM; Lenz, H-J; Gelsomino, F; Aglietta, M; Morse, MA; Van Cutsem, E; McDermott, R; Hill, A; Sawyer, MB; Cao, ZA ...
Published in: J Clin Oncol
March 10, 2018

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.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

March 10, 2018

Volume

36

Issue

8

Start / End Page

773 / 779

Location

United States

Related Subject Headings

  • Survival Rate
  • Oncology & Carcinogenesis
  • Nivolumab
  • Neoplasm Metastasis
  • Middle Aged
  • Microsatellite Instability
  • Male
  • Ipilimumab
  • Humans
  • Female
 

Citation

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Overman, M. J., Lonardi, S., Wong, K. Y. M., Lenz, H.-J., Gelsomino, F., Aglietta, M., … André, T. (2018). Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol, 36(8), 773–779. https://doi.org/10.1200/JCO.2017.76.9901
Overman, Michael J., Sara Lonardi, Ka Yeung Mark Wong, Heinz-Josef Lenz, Fabio Gelsomino, Massimo Aglietta, Michael A. Morse, et al. “Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.J Clin Oncol 36, no. 8 (March 10, 2018): 773–79. https://doi.org/10.1200/JCO.2017.76.9901.
Overman MJ, Lonardi S, Wong KYM, Lenz H-J, Gelsomino F, Aglietta M, et al. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773–9.
Overman, Michael J., et al. “Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.J Clin Oncol, vol. 36, no. 8, Mar. 2018, pp. 773–79. Pubmed, doi:10.1200/JCO.2017.76.9901.
Overman MJ, Lonardi S, Wong KYM, Lenz H-J, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine J-M, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773–779.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

March 10, 2018

Volume

36

Issue

8

Start / End Page

773 / 779

Location

United States

Related Subject Headings

  • Survival Rate
  • Oncology & Carcinogenesis
  • Nivolumab
  • Neoplasm Metastasis
  • Middle Aged
  • Microsatellite Instability
  • Male
  • Ipilimumab
  • Humans
  • Female