KEY TAKEAWAYS
- Phase III CheckMate 142 trial aimed to evaluate the efficacy of nivolumab in combination with low-dose ipilimumab as a first-line therapy for MSI-H/dMMR mCRC patients.
- The primary objective was the objective response rate evaluated by the investigator using the RECIST v1.1 criteria.
- Nivolumab was administered biweekly with low-dose ipilimumab every six weeks until disease progression.
- The patient’s objective and disease control rates were determined to be 69% and 84%, respectively, with a complete response rate of 13%.
- Out of a cohort of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 patients exhibited no progression of their condition.
- The combination of nivolumab and low-dose ipilimumab exhibited substantial and long-lasting therapeutic advantages and was well-tolerated when used as the primary therapy for MSI-H/dMMR mCRC.
Nivolumab has been granted approval by the US Food and Drug Administration for use as a monotherapy or in conjunction with ipilimumab for patients diagnosed with metastatic colorectal cancer (mCRC) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) who have experienced progression after receiving treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This decision was based on the findings of CheckMate 142. The phase II CheckMate 142 study results demonstrate the efficacy of nivolumab in combination with low-dose ipilimumab as a first-line therapy. Nivolumab was administered biweekly with low-dose ipilimumab every six weeks to MSI-H/dMMR CRC patients without prior treatment in the metastatic setting until disease progression. The principal objective was the objective response rate evaluated by the investigator using the RECIST v1.1 criteria.
The median age of the patients who received treatment was 66 years, with a sample size of 45. The median duration of follow-up was 29.0 months. The patient’s 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 a complete response rate of 13%. The median duration of response was indeterminate, with 74% of individuals exhibiting sustained responses at the time of data cutoff. The median progression-free and overall survival were indeterminate, with a minimum follow-up of 24.2 months. The 24-month progression-free and overall survival rates were 74% and 79%, respectively. A clinical benefit was observed irrespective of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. A post hoc analysis showed that out of a cohort of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 patients exhibited no progression of their condition. The patient’s self-reported outcomes remained consistent throughout treatment. 22% of patients experienced grade 3-4 treatment-related adverse events, and 13% discontinued treatment due to any grade-related adverse events. The combination of nivolumab and low-dose ipilimumab exhibited substantial and long-lasting therapeutic advantages and was well-tolerated when used as the primary therapy for MSI-H/dMMR mCRC. Based on the encouraging data, randomized studies are necessary.
Source:https://pubmed.ncbi.nlm.nih.gov/34637336/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02060188
Lenz HJ, Van Cutsem E, Luisa Limon M, Wong KYM, Hendlisz A, Aglietta M, García-Alfonso P, Neyns B, Luppi G, Cardin DB, Dragovich T, Shah U, Abdullaev S, Gricar J, Ledeine JM, Overman MJ, Lonardi S. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol. 2022 Jan 10;40(2):161-170. doi: 10.1200/JCO.21.01015. Epub 2021 Oct 12. PMID: 34637336.
