Nivolumab and low-dose ipilimumab in HER2-negative metastatic breast cancer

The NIMBUS phase II trial, recently published on Nature Communications, showed a clinical benefit and a higher response rate in highly mutated HER2-negative metastatic breast cancer treated with a dual immunotherapy regimen with nivolumab and low-dose ipilimumab.

Several lines of evidence suggest that tumors with high tumour mutational burden might respond better to dual immune checkpoint blockade and both preclinical and clinical data suggest that a combination of the anti-PD-1 nivolumab with the anti-CTLA-4 ipilimumab could activate complementary mechanisms that promote T cell antitumor activity. The NIMBUS study was a phase II trial involving 30 patients with hypermutated HER2-negative metastatic breast cancer, treated with nivolumab plus low-dose ipilimumab (1mg/kg every six weeks) for two years or until progression. The confirmed response rate was 20% and patients with a higher tumor mutational burden showed a trend towards improved progression-free survival and overall survival. Exploratory genomic analyses suggested that ESR1 and PTEN mutations may be associated with poor response, while clinical benefit was associated with a decrease or no change in tumor fraction by serial circulating tumor DNA during treatment. As authors conclude, «The study corroborates other available evidence that tumor mutational burden can serve as a clinical biomarker to broaden access to immune checkpoint inhibitors for patients with metastatic breast cancer subtypes beyond PD-L1-positive triple negative breast cancer. Additionally, we can hypothesize that patients with PD-L1-positive metastatic triple negative breast cancer and high tumor mutational burden could be treated solely with an immunotherapy-based regimen, thereby avoiding the need for concurrent cytotoxic drugs. If validated, these results could help tailor the use of immune checkpoint inhibitors among patients with high tumor mutational burden metastatic breast cancer».