Nivolumab a ‘Rising Star’ for Malignant Mesothelioma Treatment?

There may be a new treatment option on the horizon for mesothelioma patients whose cancer has come back again after treatment. Researchers in the UK are even predicting that this drug could become the new standard of care for relapsed malignant mesothelioma.

The drug is nivolumab, a PD-1 inhibitor sold under the brand name Opdivo.

Already approved for the treatment of recurrent non-small cell lung cancer, nivolumab has been shown in recent clinical trials to reduce the size of mesothelioma tumors and may even extend mesothelioma survival.

Opdivo in the News

If you think you have been hearing more about nivolumab in the news lately, you are right.

Laboratory results have suggested that this immunotherapy drug could be one of the most promising new therapies for treatment-resist malignant mesothelioma. Now, clinical studies are underway to prove it.

One such study is a Japanese phase II trial of nivolumab as an addition to first-line mesothelioma treatment along with the standard chemotherapy combination of pemetrexed (Alimta) and cisplatin.

 

Eighteen patients with unresectable pleural mesothelioma will receive the three-drug combo every 3 weeks for 4 to 6 cycles and then nivolumab by itself until their cancer progresses or side effects become too severe.

In the UK, 336 pleural or peritoneal mesothelioma patients who have received at least two prior lines of therapy are being recruited for a 12-month test of nivolumab called the CONFIRM trial. Researchers say the results could have a major impact on mesothelioma treatment protocols in the country.

“If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK,” writes lead investigator Dean Fennell of the University of Leicester.  

A recently-completed Dutch study of nivolumab for relapsed pleural mesothelioma patients produced an impressive disease control rate of 47%. In one patient, their mesothelioma tumor remained stable for a full 6 months. 

In a summary of the study in the Journal of Thoracic Oncology, the research team concludes, “Single agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pretreated patients with mesothelioma.”

Other studies of nivolumab for mesothelioma, either by itself or in combination with other agents, are ongoing at cancer centers around the world.

How Does Nivolumab Work Against Mesothelioma?

Nivolumab is a monoclonal antibody that blocks PD-1, a cell surface protein that is expressed by up to 40 percent of mesothelioma tumors. When PD-1 is blocked, the body’s immune system is better able to attack mesothelioma cells with antitumor T-cells.

In several studies of people with relapsed non-small cell lung cancer, nivolumab has been credited with extending their lives. Researchers are hopeful that the same will be true for mesothelioma patients.

Both nivolumab and pembrolizumab (Keytruda) have already been approved for head and neck cancers, colorectal cancer, and some non-small cell lung cancers.

Sources:

Quispel-Janssen, J, et al, “PD-1 blockade with nivolumab in patients with recurrent Malignant Pleural Mesothelioma”, June 13, 2018, Journal of Thoracic Oncology, Epub ahead of print

Fujimoto, N, et al, “A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol”, May 9, 2018, Clinical Lung Cancer, Epub ahead of print

Fennell, DA, et al, “CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial”, April 18, 2018, Trials