Heinz-Josef Lenz1, Eric Van Cutsem2, Maria Luisa Limon3, Ka Yeung Mark Wong4, Alain Hendlisz5, Massimo Aglietta6, Pilar García-Alfonso7, Bart Neyns8, Gabriele Luppi9, Dana B Cardin10, Tomislav Dragovich11, Usman Shah12, Sandzhar Abdullaev13, Joseph Gricar13, Jean-Marie Ledeine13, Michael James Overman14, Sara Lonardi15. 1. USC Norris Comprehensive Cancer Center, Los Angeles, CA. 2. University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium. 3. Hospital Universitario Virgen del Rocio, Sevilla, Spain. 4. Westmead Hospital, Sydney, Australia. 5. Institut Jules Bordet, Brussels, Belgium. 6. Department of Oncology, University of Torino and Candiolo Cancer Center, FPO-IRCCS, Candiolo, Italy. 7. Hospital Gral Universitario Gregorio Marañon, Madrid, Spain. 8. Universitair Ziekenhuis Brussel, Brussels, Belgium. 9. University Hospital of Modena, Modena, Italy. 10. Vanderbilt-Ingram Cancer Center, Nashville, TN. 11. Banner MD Anderson Cancer Center, Gilbert, AZ. 12. Lehigh Valley Cancer Institute, Allentown, PA. 13. Bristol Myers Squibb, Princeton, NJ. 14. The University of Texas MD Anderson Cancer Center, Houston, TX. 15. Istituto Oncologico Veneto IOV-IRCSS, Padova, Italy.
Abstract
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.
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.
Authors: Madison M Crutcher; Trevor R Baybutt; Jessica S Kopenhaver; Adam E Snook; Scott A Waldman Journal: Expert Opin Ther Targets Date: 2022-02-10 Impact factor: 6.797