The phase II GERCOR NIPICOL study evaluated 1 year of treatment with nivolumab plus ipilimumab in patients with chemotherapy-resistant metastatic colorectal cancer whose tumors were microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR). With this shortened treatment duration, 70% of patients were progression-free at 3 years in the study’s long-term follow-up reported at the 2022 ASCO Gastrointestinal Cancers Symposium.1
Romain Cohen, MD, PhD
“Results of the NIPICOL trial raise questions about the need for 2 years of therapy for all patients,” said Romain Cohen, MD, PhD, of Sorbonne University and Saint-Antoine Hospital, Paris. “And reexposure to nivolumab seems to provide additional antitumor activity for patients experiencing late resistance after discontinuation of immunotherapy.”
Based on results from KEYNOTE-1772 and CheckMate 14,2,3 immune checkpoint inhibition is the new standard of care for patients with metastatic colorectal cancer harboring MSI-H/dMMR tumors, but the optimal treatment duration remains to be determined. Treatment has involved a fixed duration of 2 years, and responses have been observed after patients have discontinued these therapies. The NIPICOL study evaluated the efficacy of a shorter treatment duration.
About the NIPICOL Trial
The study enrolled 57 patients with MSI-H/dMMR metastatic colorectal cancer previously treated with fluoropyrimidines, oxaliplatin, and irinotecan, with or without targeted therapies. Patients received nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks for four cycles, then nivolumab at 3 mg/kg every 2 weeks until disease progression or a maximum of 20 cycles (52 weeks). A second course of nivolumab was offered to patients who completed the predefined year of treatment and later developed progressive disease.
Almost half the patients had received at least three prior lines of chemotherapy; 18% had BRAF V600E mutations, and 56% had Lynch syndrome–related cancer.
The primary endpoint was the disease control rate at 12 weeks by central review of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and iRECIST (the modified version of RECIST developed for use in cancer immunotherapy trials). In their initial publication,2 the investigators explained that they used both -RECIST 1.1 and iRECIST to evaluate response, since RECIST 1.1 may underestimate response to immunotherapy due to the pseudoprogression phenomenon.
KEY POINTS
- The phase II GERCOR NIPICOL trial evaluated 1 total year of treatment with nivolumab plus ipilimumab in patients with chemotherapy-resistant metastatic colorectal cancer and MSI-H/dMMR tumors.
- The schedule involved a shorter treatment duration than is standard.
- At 3 years, 70% of patients remained progression-free.
- The findings bring into question the need for 2 years of this therapy.
In the primary analysis, the overall response rate was 59.7% as assessed by either criterion. The disease control rate at 12 weeks was 86.0% with RECIST 1.1 and 87.7% with iRECIST criteria, with one case of pseudoprogression observed.4
After a median follow-up of 18.4 months, median progression-free survival and overall survival were not reached. The 12-month progression-free survival rate was 72.9% with -RECIST 1.1 and 76.5% with iRECIST. The 12-month overall survival rate was 84%.
Updated Survival Outcomes
Dr. Cohen presented the updated survival outcomes after a median follow-up of 34.5 months (representing an additional 16 months since the last analysis). By RECIST criteria, progression-free survival rates were 75.4% at 1 year, 70.0% at 2 years, and 70.0% at 3 years. Median overall survival was not reached, and the percentage of patients alive was 84.1% at 1 year, 78.4% at 2 years, and 73.1% at 3 years. “An overall survival rate of 73% at 3 years is quite impressive in a highly pretreated population,” he commented.
The median duration of response has not been reached. At 3 years, 82.2% of patients were still responding.
A landmark analysis at 1 year included 42 patients who were free of disease progression and alive at 1 year and who were followed for a median of 35 months. In this group, the 24-month progression-free survival rate was 92.9%. Four patients had disease progression after the 1-year mark—some 8 to 17 months after initiating treatment. Three patients were retreated with nivolumab; two of them had partial responses and were alive and free of disease progression at 9 and 14 months. One had disease progression and died 9 months later, Dr. Cohen reported. “The likelihood of experiencing disease progression after 1 year of treatment is very low,” he added.
DISCLOSURE: Dr. Cohen reported financial relationships with MSD Oncology, Pierre Fabre, Exeliom Biosciences, and Amgen.
REFERENCES
1. Cohen R, Meurisse A, Pudiarz T, et al: One-year duration of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: Long-term follow-up of the GERCOR NIPICOL phase II study. 2022 ASCO Gastrointestinal Cancers Symposium. Abstract 13. Presented February 1, 2022.
2. André T, Shiu KK, Kim TW, et al: Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 38:2207-2218, 2020.
3. Overman MJ, Lonardi S, Wong KYM, et al: Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol 36:773-779, 2018.
4. Cohen R, Bennouna J, Meurisse A, et al: RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: The GERCOR NIPICOL phase II study. J Immunother Cancer 8:e001499, 2020.
