Chemotherapy, surgery and radiation have been the standard tools for treating all kinds of cancer for many years. In the recent past, however, immunotherapy in particular has started to become more important in treatment plans. Immunotherapy has been used as a solo treatment, as well as in combination with the other standards of care in the effort to find the most effective multimodal approach.
Researchers for mesothelioma have seen great promise in this emerging treatment, which stands to potentially transform the standard of care that has been largely unchanged for many years. Many clinical trials are ongoing and recruiting to study different immunotherapy drugs in combination with chemotherapy, surgery and/or radiation in the hopes of improving the often poor prognosis.
One recent study explored the possibilities of immunotherapy specifically in combination with types of radiation and chemotherapy as an effective treatment for this aggressive cancer.
Chemotherapy with Immunotherapy
Chemotherapy has long been a standard of care for mesothelioma. For many years, chemotherapy drugs cisplatin and pemetrexed (Alimta) have been the first-line recommendation. Other chemotherapy drugs have been tested individually and in various combinations as well to test their efficacy against this standard.
While chemotherapy remains a go-to treatment for this rare disease, researchers have also been experimenting more with immunotherapy. Researchers have explained that mesothelioma may be more immunogenic than originally thought, making immunotherapy a rather important tool for oncologists. Many clinical trials so far have already been starting to dig into the efficacy of immunotherapy in combination with various chemotherapy drugs.
Just last summer, the National Comprehensive Cancer Network (NCCN) revised its first-line treatment recommendation for pleural mesothelioma cases where surgery is not an option. Previously, the standard chemotherapy combination of cisplatin and pemetrexed was considered the best treatment. Now, the NCCN recommends a monoclonal antibody called bevacizumab (Avastin) in combination with these chemotherapies. Bevacizumab is a type of immunotherapy that works by blocking the formation of blood vessels that support cancerous cell growth.
The summer 2017 study also explored the use of another type of immunotherapy called checkpoint inhibitors. Checkpoint inhibitors, like anti-CTLA4 which was used in this study, work by blocking the signal between a cancer cell expressing a protein that tricks the immune system into thinking it’s a normal cell. Once that signal is blocked, the body will recognize the tumor and cancer cells as dangerous and be able to kill them.
Researchers in this study explored previous studies on these combinations and conducted their own research in mice, and concluded that chemotherapy with checkpoint inhibitors specifically could prove more effective than chemotherapy on its own.
Radiotherapy and Immunotherapy
In more recent studies, researchers are also putting a bigger focus on radiation therapy (radiotherapy) for mesothelioma and other cancers. Radiation is normally given in several small doses over the course of several days, known as fractionation. Radiation therapy technology has improved in recent years to allow doctors to give patients a higher dosage per fractionation, which also allows for a shorter course of treatment.
Researchers have found that high dose, short treatments of radiation are immunogenic and can be a good building block for immunotherapy as a secondary treatment. Those involved with this most recent study believe that this type of radiotherapy in combination with checkpoint inhibitors could better eliminate tumors in mesothelioma patients and be an effective treatment before surgery.
The researchers state that radiotherapy given in this manner has an immunogenic effect, with T cells becoming activated by the tumor cells’ antigens and thus moving to the tumor site to destroy the cancerous cells. As such, the researchers saw this as a good opportunity to introduce checkpoint inhibitors to the system to further improve immune response and optimize the results of radiation and surgery.
Again, these researchers used a CLTA-4 blockade in this test with mice to see if it would induce a similar delay in tumor growth as it had in combination with chemotherapy. With local radiation and the anti-CTLA-4 inhibitor, the researchers found a better T cell response in infiltrating and delaying tumor cell growth. Though they explain further study will be needed, this experiment shows radiation and immunotherapy together can help produce more effective results in surgery than radiation alone pre-surgically.
More Research in Immunotherapy
Ultimately, the researchers found immunotherapy can be a powerful addition to standard treatments and further improve the efficacy of patient care. Though their studies did not include human interaction at this point, there have been many other clinical trials that have shown similar promising results among many patient groups.
Overall, immunotherapy is becoming increasingly important for research in mesothelioma and other cancers, and has the potential to transform how doctors approach cancer treatment in the future.