TY - JOUR
T1 - First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/ Mismatch Repair-Deficient Metastatic Colorectal Cancer
T2 - The Phase II CheckMate 142 Study
AU - Lenz, Heinz Josef
AU - Van Cutsem, Eric
AU - Limon, Maria Luisa
AU - Wong, Ka Yeung Mark
AU - Hendlisz, Alain
AU - Aglietta, Massimo
AU - García-Alfonso, Pilar
AU - Neyns, Bart
AU - Luppi, Gabriele
AU - Cardin, Dana B.
AU - Dragovich, Tomislav
AU - Shah, Usman
AU - Abdullaev, Sandzhar
AU - Gricar, Joseph
AU - Ledeine, Jean Marie
AU - Overman, Michael James
AU - Lonardi, Sara
N1 - Publisher Copyright:
© 2021 by American Society of Clinical Oncology.
PY - 2022/1/10
Y1 - 2022/1/10
N2 - PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.
AB - PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.
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U2 - 10.1200/JCO.21.01015
DO - 10.1200/JCO.21.01015
M3 - Article
C2 - 34637336
AN - SCOPUS:85123389652
SN - 0732-183X
VL - 40
SP - 161
EP - 170
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -