“There’s no question that research cures cancer,” began Dr. Rich Alexander of the University of Maryland and chair of the Meso Foundation’s Board of Directors. “If you look at the most effective therapies that we have now for many cancers across the country, those treatments were defined through the clinical trials process.”
At the 2017 International Symposium on Malignant Mesothelioma, Dr. Alexander gave a joint presentation with Dr. Tobias Peikert of the Mayo Clinic and chair of the Meso Foundation’s Science Advisory Board, in which they provided attendees with a recap of what was discussed in the exclusive science session that was held concurrently to the general session during the Symposium.
Collaboration was a key theme. “We had a lot of discussions about how to move mesothelioma research forward in a collaborative fashion,” says Dr. Peikert. “I think there are some great collaborations and opportunities for collaborations that are actually evolving in regards to the science of mesothelioma and especially mesothelioma clinical trials.”
A lot of promising data was presented in regards to radiation therapy. Dr. Peikert made note of the better radiation approaches that are now available, including intensity-modified ration therapy, proton beam therapy, and now radiation therapy is sometimes given before surgery. The amount of radiation that works best when given before surgery is still not clear. In order to determine this, researchers look for an abscopal effect, which is a when radiation therapy drives an immune response (for example, when treating tumors locally, in addition to the shrinking of the tumor directly treated with radiation, shrinking of tumors not treated is also observed due to the body’s immune response). Dr. Marc de Perrot, University of Toronto, presented data from his study in which he showed through an animal model that by using radiation therapy prior to surgical removal of the tumor followed by a seven day waiting period, a robust immune response was induced. This type of response makes a difference in regards to the outcome after surgery.
Much excitement is also evident around advances in immunotherapy, including clinical trials that use checkpoint inhibitors. Dr. Hedy Lee Kindler, University of Chicago, presented an update on her data using checkpoint inhibitors in patients with mesothelioma. Interesting response rates are also being seen in trials using CTLA-4 blocking antibodies in combination with PD-L1 blocking antibodies. Other immunotherapies being studied are not checkpoint inhibitors, specifically CAR T-cells, which are bioengineered T-cells that can target the tumor.
“I think where we need to go is to really try to understand this landscape a little bit better and actually personalize these treatments,” says Dr. Peikert. “I don’t think there’s going to be a one-size-fits-all type of immunotherapy.” It will be important to better identify biomarkers and to be able to understand who is going to respond to which type of treatment.
In addition to advances in immunotherapy, targeted therapies were also discussed during the session, which are primarily focused on synthetic lethality. As researchers develop a better understanding what is happening in the tumors, they can understand what pathways the tumors rely on to live. Promising data is also being seen in mesothelin-targeted therapies. Some animal data has shown positive results with the use of mesothelin-targeted therapies in combination with chemotherapy drugs, specifically Paclitaxel, or immunotherapy. Dr. Raffit Hassan, National Cancer Institute (NCI), is currently starting a clinical trial at the NCI that uses Paclitaxel in combination with an immunotoxin.
Clinical Trials Continue to Be the Way Forward
One of the most important things moving forward, Dr. Peikert notes, is getting patients into clinical trials. This includes not only mesothelioma patients, but all patients across the spectrum of thoracic malignancies and cancer in general. Dr. Peikert expresses the need for a better clinical trials network and more multicenter trials in order to make them more accessible to the patient population.
IASLC and NCI Partnerships
“The Meso Foundation has elevated the profile of mesothelioma research around the world,” notes Dr. Alexander. The Foundation has now partnered with the International Association for the Study of Lung Cancer (IASLC), which will provide more exposure to mesothelioma research at IASLC’s annual meeting that is attended by thousands of experts in the field of lung cancer.
IASLC’s leadership, specifically CEO Dr. Fred Hirsch, has made mesothelioma an active disease group within the organization. “I think this is a great opportunity,” says Dr. Peikert. It will allow doctors and researchers in the mesothelioma field to actually present their science on a larger platform and discuss their work with a broader group of experts.
Additionally, the Meso Foundation, IASLC, and the NCI have formed a task force meant to prioritize mesothelioma research and identify areas of research to support. The task force, which includes many of the experts who presented at the Symposium, met at the NCI the day after the conference with the goal of designing two clinical trials, one for early-stage disease and one for advanced-stage disease.
Peritoneal Mesothelioma Update
Dr. Alexander specializes in the treatment of peritoneal mesothelioma, and he led the peritoneal working group at the Symposium. Peritoneal mesothelioma is the more rare form of the disease; it has a different biology, it behaves differently, and it is treated differently in some respects. Dr. Alexander notes that there has never been agreement on how the field should move forward, but significant progress was made during the working group.
“At this meeting, we have agreed to work together collaboratively to form a peritoneal mesothelioma task force and to conduct a multicenter prospective research trial, and we have a framework for that,” says Dr. Alexander. The group’s intention is to have a randomized clinical trial set up within the next year that will allow them to compare two arms of peritoneal mesothelioma treatment that are commonly used around the country. One arm of treatment will be intravenous chemotherapy and the other will be intraperitoneal chemotherapy. There will not be a placebo, but rather the two treatments will be tested in a controlled setting to determine if one results in a better outcome than the other.
In the peritoneal field, researchers are also looking at ways to improve imaging and better ways of classifying the tumor histologically to be able to better understand how the tumor is likely to behave in an individual’s body.
“I think the most exciting thing that I take away from this conference is that we, as researchers, need to work on moving some of this exciting pre-clinical data actually into clinical practice and try to increase the participation of patients in clinical trials and perhaps actually build these clinical trials networks,” Dr. Peikert concludes.