Nivolumab plus ipilimumab serve promising dual checkpoint inhibition

Dual checkpoint inhibition with nivolumab plus ipilimumab may be a promising treatment option for patients with HER2-negative metastatic breast cancer and high tumour mutational burden (TMB).

In the open-label, multicentre, phase 2 NIMBUS trial (NCT03789110), the efficacy and safety of dual checkpoint inhibition with nivolumab plus low-dose ipilimumab was evaluated in patients with hyper-mutated breast cancer with a TMB≥9 mutations/megabase (mut/Mb). Dr Romualdo Barroso-Sousa (Hospital Sírio-Libanês, Brazil) presented the results [1].

The NIMBUS study included 30 patients with HER2-negative metastatic breast cancer (70% HR-positive, 30% triple-negative breast cancer) and a TMB of at least 9 mut/Mb (median 10.9 mut/Mb). The median number of prior chemotherapy lines was 1.5 and the maximum was 3. Patients received nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity, or up to 24 months.

During a median 9.7 months of follow-up, there were 5 (16.7%) confirmed objective responses, all of which were partial. A further 6 (20%) patients had stable disease during follow-up. Median duration of response was 12.1 months, while median progression-free survival and overall survival were a respective 1.4 and 19.3 months. Exploratory analyses revealed that in patients with a high TMB (≥14 mut/Mb) the overall response rate was 60% versus 8% in the 25 patients with a TMB of 9–13 mut/Mb. Median progression-free survival and median overall survival was 9.5 months and not reached in patients with a TMB≥14 mut/Mb versus 1.4 months and 8.8 months in patients with a TMB of 9–13 mut/Mb.

Based on these results, Dr Barrosso-Sousa concluded that: “this study supports the use of checkpoint inhibitors among patients with HER2-negative metastatic breast cancer and TMB. However, the study does not answer the question whether dual checkpoint inhibition is better than pembrolizumab monotherapy.”

1. Barroso-Sousa R, et al. Nimbus: A phase 2 trial of nivolumab plus ipilimumab for patients with hypermutated her2-negative metastatic breast cancer (MBC). GS2-10, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022