A small group of Australian mesothelioma patients have reportedly lived more than twice as long as expected with a combination of standard chemotherapy and immune system manipulation with the CD40 protein.
The CD40 protein plays a role in a broad range of immune and inflammatory responses in the body. Studies in mice have found that activating CD40 with an activating antibody may work “synergistically” with chemotherapy drugs to fight cancer.
To see whether CD40 activation could produce a similar response in human patients, researchers with the University of Western Australia and Sir Charles Gairdner Hospital in Perth recruited 15 malignant pleural mesothelioma patients in the early stages of the disease. The patients all received both standard chemotherapy (pemetrexed and cisplatin) and the CD40 activating antibody CP-870,893.
Patients received 75 mg of cisplatin and 500 mg of pemetrexed on the first day of their mesothelioma treatment. On the eighth day, researchers added a dose of CP-870,893. Depending on the response, patients could have up to 6 subsequent cycles of just CP-870,893. Changes in their immune system response were monitored throughout the treatment process.
The response for most of these mesothelioma patients was about the same as others treated with just pemetrexed and cisplatin. Six patients (40%) experienced some shrinkage in the size of their mesothelioma tumors while nine (53%) experienced temporary stability in the growth of their tumors. Median overall survival was 16.5 months and the median time before mesothelioma tumors started growing again was 6.3 months.
But the best news from the study is that three of the mesothelioma patients on the combination treatment lived another two-and-a-half years after treatment. This is considered “long-term survival” since few mesothelioma patients live more than a year beyond diagnosis. The authors conclude that, although it is no miracle cure for mesothelioma, the addition of up to 0.15 mg/kg of CP-870,893 to standard chemotherapy is “safe and tolerable” and could significantly extended survival in some patients.
Nowak, AK, et al, “A phase 1b clinical trial of the CD40 activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma”, September 18, 2015, Annals of Oncology, Epub ahead of print