Opdivo for Malignant Mesothelioma: Could a Lower Dose Work?

There is new evidence that low doses of the drug Opdivo (nivolumab) may extend lung cancer survival as well as the standard dose—at a much lower cost. The news may have implications for people with the lung-related asbestos cancer, malignant mesothelioma, who are also sometimes treated with Opdivo.

Pleural mesothelioma is a hard-to-treat cancer that grows on the lining around the lungs and causes many of the same symptoms as lung cancer.

Some evidence has suggested that Opdivo, an immunotherapy drug already approved for the treatment of recurrent lung cancer, may soon become the first drug approved for recurrent mesothelioma, too.

Now, a newly-published Korean study finds that patients may not need as much of the drug as originally thought to experience life-saving results.

Standard Dose Opdivo Versus Low Dose

Opdivo 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.

Typically, lung cancer patients on Opdivo receive 3 mg/kg (or a fixed dose of 240 mg) every 2 weeks. But, like many experimental treatments, Opdivo can be very expensive. Although many drug companies offer financial assistance programs for high-priced drugs like Opdivo, for some patients, they remain out of reach.

In an effort to come up with a solution to what they call “financial toxicity”, researchers at Seoul National University College of Medicine experimented with giving a small group of recurrent non-small cell lung cancer patients just 100 mg of Opdivo every 3 weeks.

Among 47 patients, 18 received the lower dose while the rest received the standard dose.

“During 5.2 months of follow-up, the objective response rate was 13.8% in the standard-dose group and 16.7% in the low-dose group,” reports study author Shin Hye Yoo. “Dosing of nivolumab or PD-L1 expression did not significantly affect progression free survival or overall survival.”

The researchers conclude that the lower-dose regimen is “worth considering” as an alternative to more expensive treatments and deserves further study.

Studies of Opdivo in Mesothelioma Treatment

Meanwhile, Opdivo is currently the focus of multiple mesothelioma studies.

Japanese researchers are conducting a phase II trial of nivolumab as an addition to first-line mesothelioma treatment with the standard chemotherapy combination of pemetrexed (Alimta) and cisplatin.

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 Opdivo which could have a major impact on mesothelioma treatment protocols in the country.

And in The Netherlands, a recently-completed study of single-agent Opdivo for recurrent pleural mesothelioma produced a promising disease control rate of 47 percent. In one patient, his mesothelioma was stable for six months.

Sources:

Yoo, SH, et al, “Low-dose nivolumab can be effective in non-small cell lung cancer: alternative option for financial toxicity”, July 25, 2018, ESMO Open

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