NIPICOL: New data on optimal ICI treatment duration in MSI/dMMR mCRC

Nivolumab maintenance therapy after nivolumab plus ipilimumab induction therapy, with a fixed treatment duration of 1 year, demonstrated to be efficacious in patients with microsatellite instability-high (MSI-h)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC). The current phase 2 NIPICOL trial displayed that 2 years of therapy may thus not be needed for all patients in this population [1].

Dr Romain Cohen (Sorbonne University, France) explained that immune checkpoint inhibitors are the new standard-of-care for patients with MSI/dMMR mCRC. “Mostly, a fixed duration of 2 years of therapy is applied. However, maintained responses have been observed, despite treatment discontinuation in this population [2]. Therefore, the optimal treatment duration remains to be established.” The multicentre, single-arm, phase 2 NIPICOL trial (NCT03350126) exposed patients with MSI/dMMR mCRC to nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) induction therapy, every 3 weeks, 4 cycles, followed by nivolumab maintenance therapy (3 mg/kg), every 2 weeks, maximum 20 cycles, constituting a treatment duration of 1 year. The primary analysis showed that the 12-week disease control rate, the primary endpoint of this study, was 86.0% (RECIST 1.1).

After an additional 16 months of follow-up, the 3-year progression-free survival rate was 70.0% and the 3-year overall survival rate was 73.1%. Moreover, after 34.5 months of follow-up, the median duration of response was still not estimable. A landmark analysis at 1 year, including 42 patients free of progression, displayed a 24-month median PFS rate of 92.9%. Furthermore, data in 4 patients who were re-treated with nivolumab after disease progression suggested that re-exposure to this agent may add additional anti-tumour activity in patients who experienced late resistance after immunotherapy treatment discontinuation. However, further studies with larger sample sizes are warranted to investigate this matter.

Dr Cohen concluded that the efficacy of the currently investigated 1-year fixed duration nivolumab and ipilimumab treatment regimen questions the need for 2 years of therapy in all patients with MSI/dMMR mCRC. “We need to develop tools to distinguish patients who require longer treatment duration from those who may be eligible for 1 year of therapy.” This will also be important from an economic perspective.

1. Cohen R, 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 2 study. Abstract 14, ASCO GI 2022, 20–22 January.
2. Overman MJ, et al. J Clin Oncol. 2018;36(8):773–779.

 

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Posted on 21 March 202217 May 2024