Opdivo May Improve Survival in Mesothelioma That Progressed on First-Line Chemotherapy

Immunotherapy with Opdivo (nivolumab) may be a beneficial treatment for patients with malignant mesothelioma whose disease progressed on first-line therapy, trial results demonstrated.

“Immunotherapy had demonstrated potentially useful activity in patients with mesothelioma who had growth of their tumors after initial (first-line) chemotherapy,” said Dean A. Fennell, a professor of thoracic medical oncology and director of a mesothelioma research program at the University of Leicester in the United Kingdom, in an interview with CURE®. “No treatment to date (has) been licensed for the treatment of these patients. This is therefore a clinical setting of unmet need.”

Findings from the CONFIRM trial were published in Lancet Oncology, which represents “the first phase 3 clinical trial to have demonstrated an improvement in survival for patients with relapsed mesothelioma,” said Fennell, who was one of the researchers on this trial.

Although Opdivo on its own may provide an effective treatment option for patients with malignant mesothelioma, it has not been approved by the Food and Drug Administration (FDA) for this particular use. Of note, Opdivo has been approved with another immunotherapy for patients with malignant mesothelioma.

“It is important to note that immunotherapy with (Opdivo) and ipilimumab (Yervoy) was approved by the FDA,” Fennell said. “This treatment is therefore a first-line option for patients worldwide. As with other cancers, immunotherapy is likely to find its home for patients in the first-line setting.”

In the CONFIRM trial, researchers assessed data from 332 patients with relapsed, malignant mesothelioma. These patients were randomly assigned treatment with Opdivo (221 patients; median age, 70 years; 76% men) or placebo (111 patients, median age, 71 years; 78% men). Both groups received treatment every two weeks until disease progression or a maximum of 12 months, whichever occurred first.

The main objectives of this trial were to assess progression-free survival (time from treatment assignment to disease progression or death) and overall survival (time from treatment assignment to all-cause death). Patients were followed up for a median of 11.6 months.

During the trial, patients received a median of six doses of Opdivo and four doses of placebo. Patients assigned Opdivo had a median progression-free survival of three months compared with 1.8 months in those assigned placebo. In addition, median overall survival was 10.2 months in the Opdivo group versus 6.9 months in the placebo group.

The most commonly reported severe or worse side effects related to the treatment in patients assigned either Opdivo or placebo included diarrhea (3% versus 2%, respectively) and infusion-related reactions (3% versus 0%, respectively). Serious side effects occurred in 41% of patients in the Opdivo group compared with 44% in the placebo group. No deaths related to the treatment occurred in either group.

“The toxicity of (Opdivo) was in line with expected, licensed therapy,” Fennell said. “(Side effects) due to (Opdivo) were manageable. It should be noted that overall, the serious (side effect) rate was higher for patients receiving placebo rather than (Opdivo). This reflects the general safety of this treatment that was well tolerated.”

Despite these important findings, Fennell mentioned that more research is needed in this area.

“It’s essential that we understand why patients with mesothelioma respond at all to immunotherapy,” he said. “Understanding this could help us personalize therapy (improve cost effectiveness and efficacy); develop better combinations to improve the level of expected benefit for patients; and develop immunotherapies that can overcome resistance that develops with first-line therapy.”

Fennell noted that new treatments for patients with mesothelioma represent an exciting time in this space.

“New treatments for mesothelioma are being reported at an increased rate, which is very welcome with associated approvements in clinical outcome,” he concluded. “This is very welcome and is set to continue as we increase our understanding of biology and evaluate more new exciting treatments, particularly in the relapsed setting where there remains a lack of FDA-approved therapy.”

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