If you live In the United States where pharmaceutical companies advertise directly to consumers, in the last few years you’ve likely seen many ads for drugs whose unbranded names end in “mab.” Many of the advertised drugs are used to treat disorders such as rheumatoid arthritis, Crohn’s disease, psoriasis, asthma, Alzheimer’s disease, to mention a few.
Mesothelioma patients and their families may also have noticed that the names of the immune checkpoint inhibitor drugs recently making news also end the same way (i.e. pembrolizumab and nivolumab respectively known by trade names of Keytruda and Opdivo), which means they’re all part of the same family. But how can one family of drugs work for disorders so different from one another? What could they possibly have in common? The answer is: the immune system. Put (very) simply, when treating diseases in which the immune system is attacking its own tissues, these drugs are engineered to turn off those particular immune processes. In turn, when treating cancers such as mesothelioma, these drugs turn the immune system on and aim it toward the cancer cells.
In mesothelioma in particular, these drugs are known as PD-1 and PD-L1 inhibitors, because they target that particular protein.
As Dr. Kristen A. Marrone, a medical oncology fellow at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital explained in our summer newsletter, “PD-1 is an immune checkpoint found on an immune cell called a T-cell, and inhibits (stops) normal T-cell function when it is turned on by another immune checkpoint protein called PD-L1. PD-L1 has been found on many different kinds of cancer cells, including mesothelioma, and is thought to be one way that these cancer cells can turn off the normal immune response that would otherwise harm them.”
“These immune checkpoint inhibitors are commonly well-tolerated, with fewer side effects than classic chemotherapy. However, because they turn on your immune system, they can cause unique side effects related to autoimmune diseases, where your immune system can attack your normal tissue/organs,” added Dr. Marrone.
Most recent results for these types of drugs targeting mesothelioma were presented less than two months ago at the World Conference on Lung Cancer (each of these studies has a different design and measures effectiveness at different intervals so it is not advisable to compare them directly to one another). In particular, a Phase II study of nivolumab (Opdivo) showed a disease control rate of 80% in the 15% of patients who responded to treatment. There were no complete responses in the 34 patients enrolled in the study. Partial responses were seen in all groups of patients regardless of PDL1 expression. The median progression-free survival in this study was 110 days.
An interim analysis of a phase II trial of pembrolizumab (Keytruda) reported a disease control rate of 80% for the 21% of patients who showed a response to the drug. There were no complete responses. The median progression-free survival was 6.2 months.
Finally, a study on long-term overall survival of patients on pembrolizumab (Keytruda) showed a disease control rate of 72% in the 20% of patients who responded to treatment. Progression-free survival was 5.4 months. Only this last study was mature enough to reach the median duration of response, which was at 12 months.
Anna Nowak, MD, PhD, a researcher and clinician at the University of Western Australia in Perth, with expertise in immunotherapy, helped us put some of these data into perspective.
“The results so far are good, and provide hope to many, but they are not nearly good enough. While small clinical trials have shown that around 20% of people with mesothelioma have durable responses to immunotherapies such as pembrolizumab and nivolumab, we must remember that the other 75-80% of people do not respond,” said Dr. Nowak.
“The contribution of stable disease remains unclear, as many people with mesothelioma can have stable disease over 6 to 9 weeks without any treatment. It is critical that we continue to explore, in randomized trials, the role of biomarkers, patient selection, combination immunotherapies, and combinations with chemotherapy for the benefit of the other 80% of people who do not respond to these types of treatments,” she added.