The most recent installment of the Meso Foundation’s “Meet the Mesothelioma Experts” series is now available for listening on our website. The session was held on May 14 with Dr. Evan Alley of the University of Pennsylvania. During the call, Dr. Alley was interviewed by Mary Hesdorffer, the Meso Foundation’s executive director and experienced nurse practitioner. He discussed his new clinical trial for pleural mesothelioma patients, which is looking into an agent that would inhibit the PD-L1 protein.
PD-L1 is a protein believed to play a role in suppressing the immune system. Generally, it is associated with pregnancy and autoimmune diseases. In cancer, a high tumor expression of PD-L1 is linked with more aggressive disease and a poorer prognosis. Research into PD-L1 inhibitors has already shown much promise in melanoma, renal cell carcinoma and lung cancer, evidencing both tumor shrinkage and durable response, and prompting a number of mesothelioma centers to open trials testing similar agents.
Dr. Alley is part of the Penn Mesothelioma and Pleural Program team and the interim chief of the Division of Hematology and Medical Oncology at Penn Presbyterian Medical Center.
You can listen to the session with Dr. Alley, as well as past “Meet the Mesothelioma Experts” session here.
Today, MolMed, an Italian pharmaceutical company, released results from its NGR-hTNF for mesothelioma clinical trial. While the trial, which enrolled 400 pleural mesothelioma patients, demonstrated no increases in overall survival of the entire population, it did show an improvement in survival for those patients with a poorer prognosis and whose disease had progressed between first-line chemotherapy and the start of the trial.
Moreover, for this latter group of patients, researchers observed a 40% longer progression-free survival.
Dr. Julie Brahmer, who led the trial at Johns Hopkins (this was a worldwide trial), said that “it is great to see a survival advantage with the addition of a new drug in combination with chemotherapy for mesothelioma.” She added that, “unfortunately the study was not positive for the overall population. It is unclear why this subpopulation would benefit and the whole population would not. I look forward to the full presentation of the results.
“This study is the first of its kind in mesothelioma, and may provide a new treatment option for patients who had cancer growth after standard chemotherapy,” said Lee Krug, MD, the chair of the Board of Directors of the Meso Foundation, and thoracic oncologist at Memorial Sloan-Kettering Cancer Center.
More information is available through this press release by MolMed.
The Meso Foundation previously wrote about this clinical trial, and discussed the NGR-hTNF clinical trial in one of its “Meet the Mesothelioma Experts” broadcast.
The most recent installment of the Meso Foundation’s “Meet the Mesothelioma Experts” series is now available for listening on our website. The session was held on April 8 with Dr. Joanna C. Horobin, the Chief Medical Officer at Verastem, Inc. Dr. Horobin discussed the company’s latest investigational agent, defactinib, which is being developed for use in patients with pleural mesothelioma.
During the call, Dr. Horobin was interviewed by Mary Hesdorffer, the Meso Foundation’s executive director and experienced nurse practitioner. The session focused on learning more about investigational agent defactinib, which is used to delay the time to progression after having a response or stabilization with first-line therapy.
Dr. Joanna C. Horobin, M.B., Ch.B, has been the Chief Medical Officer at Verastem, Inc. since October 2012.
You can listen to the session with Dr. Horobin, as well as past “Meet the Mesothelioma Experts” session here.
It was recently reported that a clinical trial that randomized patients to receive hypnosis and cognitive therapy had a statistically significant reduction in their fatigue levels as compared to 79 percent of patients who did not have this intervention. The sudy was led by Guy Montgomery, PhD, Director of the Integrative Behavioral Medicine Program at Mount Sinai Hospital in New York.
Two hundred breast cancer patients who were undergoing radiation therapy were eligible to participate in this study. It was unusual to find that six months after the completion of radiation therapy, the intervention group reported less fatigue than 95% of the control group (patients who did not receive hypnosis and cognitive therapy). Mesothelioma patients often receive radiation therapy following the completion of an extrapleural pneumonectomy (EPP) or a Pleurectomy Decortication (PD). Though there are no studies currently underway in mesothelioma, it seems reasonable that patients who will be undergoing surgery plus radiation should be put in touch with integrative medicine to ascertain what services might be available to them.
A few years back, we invited a hypnotherapist to conduct a workshop at the Meso Foundation’s Symposium to aid the community in banishing negative thoughts usually implanted during the initial diagnosis when they were informed of the disease and prematurely provided with a prognosis from a doctor unfamiliar with mesothelioma. A positive outlook certainly does not cure the disease, but patients who are positive tend to eat better, engage with others, and less often fall victim to depression, which could impact their ability to function.
The study, recently published in the Journal of Clinical Oncology (2014; doi:10.1200/JCO.2013.49.3437
by Tao Dao, Lee M. Krug and David A. Scheinberg, Memorial Sloan Kettering Cancer Center, New York, NY
Wilms’ tumor 1 (WT1) is a protein that is present at high levels in many types of cancers (especially mesothelioma), but it is generally not found in normal cells. Therefore, we think that it is a potential target for novel therapies, and particularly immunotherapies. WT1 is typically found inside the cell, in the nucleus. Only after it is processed and moved to the surface of the cancer is it possible for the immune system to see it. We think that if we could teach the immune system to attack WT1, we could find an effective way to specifically kill mesothelioma cancer cells.
At Memorial Sloan Kettering Cancer Center, we are studying two ways to boost the immune response against WT1. The first is with a vaccine. Normally, the WT1 protein does not cause an immune response to occur. However, we found that small pieces of WT1 proteins that are just slightly different from normal WT1 protein can stimulate the immune system better. If we can teach the patient’s immune system to target WT1 using a vaccine made up of these protein pieces, then perhaps it will also learn to attack the cancer cells. In fact, when we gave the WT1 vaccine to patients along with some immune booster medicines, they developed an excellent immune response specifically to WT1. We are now studying this vaccine in a larger clinical trial to see if it is effective against the cancer. Patients who have undergone surgery for mesothelioma either get the immune boosters alone or together with the WT1 vaccine to see if it can prolong the time before the mesothelioma grows back.
We are now also studying another way to attack WT1 using antibodies. Antibodies are proteins in the body that stick to foreign substances (such as bacteria or viruses) and tag them for destruction by the immune system. In this case, however, we have engineered antibodies in a laboratory so they will recognize WT1. Thus, instead of the vaccine strategy which relies on teaching the patient’s immune system to attack WT1, these antibodies can be injected and bind directly to it. We have demonstrated that this antibody is a potent therapeutic agent against human mesothelioma in animal models. Our study was published in the Science Translational Medicine in March, 2013. (http://stm.sciencemag.org/content/5/176/176ra33.long). We are working to bring this promising new drug to clinical application in the very near future.
We greatly appreciate the grant support from the Mesothelioma Applied Research Foundation for our exciting research targeting WT1 by both vaccines and antibody therapies (TD and LMK are recipients of Meso Foundation grants).