A study of the PD-L1 inhibitor nivolumab showed “safety and efficacy” in mesothelioma patients who failed with other treatments.
Nivolumab is a type of immunotherapy marketed under the brand name Opdivo. It is similar to pembrolizumab (Keytruda) in that it blocks the tumor-promoting protein PD-L1. Nivolumab is most often used for patients with non-small cell lung cancer.
A multicenter phase II Japanese study found the PD-L1 inhibitor nivolumab helped a group of pleural mesothelioma patients live longer. Just as importantly, the side effects of the drug were “manageable”.
Human Trial of PD-L1 Inhibitor Nivolumab
Chemotherapy with pemetrexed (Alimta) and cisplatin is the standard first-line treatment for pleural mesothelioma. But many patients either do not respond to chemotherapy or they stop responding after a while. There is no approved second-line treatment for mesothelioma.
When the standard treatment stops working, doctors usually look to drugs that are approved for other types of cancer. The PD-L1 inhibitor nivolumab is not FDA-approved for pleural mesothelioma. But some laboratory studies suggest it might be a viable option. The next step was to test it in human mesothelioma patients.
Mesothelioma Immunotherapy with Opdivo
Opdivo is a type of immunotherapy. That means it harnesses the power of the immune system cells to fight cancer. The Japanese trial was called MERIT. In MERIT, patients received the PD-L1 inhibitor nivolumab by itself as a second- or even third-line therapy.
PD-L1 helps mesothelioma tumors grow by making it harder for the immune system to detect them. The theory is that the higher the PD-L1 level, the easier it is for the tumor to hide. Patients in the MERIT trial received 240 mg of Opdivo every two weeks until their mesothelioma either progressed or they got too sick to continue.
PD-L1 Level and Drug Effectiveness
The Japanese researchers wanted to see how the MERIT patients’ PD-L1 levels impacted how well the drug worked. Of the 34 pleural mesothelioma patients tested, almost 60 percent of them had elevated levels of the protein.
Ten of the 34 patients (29.4%) responded to treatment with the PD-L1 inhibitor nivolumab. But there was a big difference between the people with high PD-L1 levels and the rest of the patients. Forty percent of the mesothelioma patients with elevated PD-L1 responded. The rate was only 8.3 percent for people with normal PD-L1 levels.
“Single-agent nivolumab showed efficacy and safety in 2nd/3rd line patients with malignant pleural mesothelioma,” concludes the report. “There were higher responses in PD-L1 positive patients.”
Other studies of the PD-L1 inhibitor nivolumab are ongoing. In the UK, more than 300 previously-treated mesothelioma patients are in a trial called CONFIRM. It is the first double-blind placebo-controlled phase III trial of Opdivo for mesothelioma. The results could change mesothelioma treatment 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,” said lead investigator Dean Fennell of the University of Leicester.
AOE, K, “A phase II study of nivolumab: a multicenter, open-label, single arm study in malignant pleural mesothelioma (MERIT)”, Epub, January 7, 2020, Annals of Oncology, https://www.ncbi.nlm.nih.gov/pubmed/32177423
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