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SAN ANTONIO -- A small percentage of heavily pretreated patients with hypermutated HER2-negative metastatic breast cancers had durable responses from treatment with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy), a researcher reported.

In a phase II trial that sought patients with these types of tumors -- representing about 10% of all metastatic breast cancers -- five of 30 responded, for an objective response rate of 16.7%, which was within the achievement goal of the so-called trial, said Romualdo Barroso-Sousa, MD, PhD, of Hospital Sírio-Libanês in Brasília, Brazil, during an oral presentation at the .

Four of the five individuals had durable responses that lasted longer than a year, Barroso-Sousa said, adding that two of these patients had to discontinue treatment because of tolerability issues, but still maintained objective responses for 16 and 25 months, respectively.

Median progression-free survival was 1.4 months, while median overall survival was 19.3 months, Barroso-Sousa reported.

"This study supports the use of checkpoint inhibition for patients with HER2-negative metastatic breast cancer and high tumor mutation burden regardless of hormone receptor status, but does not answer the question of if dual inhibition is better than pembrolizumab [Keytruda] monotherapy," he noted.

The NIMBUS (Nivolumab Plus Ipilimumab in Metastatic Hypermutated HER2-Negative Breast Cancer) study built on previous research in solid tumors -- which included breast cancer patients – that indicated that cancers with high tumor burden were sensitive to immunotherapy, he explained. "While patients with a tumor mutation burden greater than or equal to 14 [per megabase] were a minority in this study, they did achieve an objective response of 60%."

The 14 mutations per megabase cutoff was one of the prespecified secondary endpoints in the study, although the main cutoff in the trial was nine mutations per megabase. "Further work is needed to investigate the optimal tumor mutation burden cutoff for selecting patients to receive checkpoint inhibition," Barroso-Sousa said.

Tufia Haddad, MD, of the Mayo Clinic in Rochester, Minnesota, commented: "The goal of this trial -- to have 10% to 20% of the patients respond to the therapy -- is reasonable. The trial also includes genetic testing as standard of care, so that we can identify the 10% with these high tumor mutation burdens and we can give these patients with advanced disease new agents that can extend their lives."

However, the NIMBUS trial is unlikely to immediately change clinical practice, she told 名媛直播. "This combination of nivolumab and ipilimumab remains investigational in this patient population, but it is encouraging to see this response rate, and if you are lucky enough to be one of those people, you are going to get a really, really durable response."

Barroso-Sousa explained that NIMBUS was an investigator-initiated, multicenter single-arm trial of patients diagnosed with metastatic HER2-negative breast cancer, who could have received up to three lines of prior therapy; 73% of those enrolled had undergone previous treatment for metastatic disease. Participants had to have measurable disease.

Patients received a combination of nivolumab at 3 mg/kg every 2 weeks and low-dose ipilimumab at 1 mg/kg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months of treatment duration. Restaging scans were performed every 6 weeks for the first 6 months and then every 9 weeks thereafter.

Adverse events were similar to what has been previously seen in other tumor histologies with the combination of nivolumab and ipilimumab, said Barroso-Sousa. There were no grade 4 or 5 events, and the most common adverse events were fatigue, diarrhea, anemia, and anorexia.

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