Mesothelioma: No Cure Yet, But Much Promise in New Therapies

Clinical Trialsby Mary Hesdorffer, NP, Executive Director of the Meso Foundation

Mesothelioma has often been referred to as a cancer resistant to chemotherapy. That attitude changed when in 2004, the combination of Alimta and Cisplatin demonstrated a survival advantage over Cisplatin alone. This was a large randomized study that paved the way for pharmaceutical companies to become interested in this disease often thought to be recalcitrant.

Today, rather than telling our patients to go home and get their affairs in order, we can instead provide them with a wide array of treatment options, whether first diagnosed, after a recurrence, or even after several prior regimens.

Having options is an incredible step forward in this cancer that even merely a decade ago was seen as hopeless. But with options also come some challenges.

One such challenge is the healthcare providers’ lack of time necessary to fully inform patients with mesothelioma about their options. For this reason, providers will often present only a few of the many options to their patients.

Patients are fortunate that some providers unable to fully perform this task are referring their patients to the Mesothelioma Applied Research Foundation. At the Meso Foundation, a dedicated nurse practitioner spends the necessary time to go through the options, taking into account insurance coverage, stage of disease, histology and readiness to participate in a clinical trial.

The initial presentation and consultation during this stage is often complicated by the physical, emotional and legal challenges associated with the diagnosis. Patients and family members are often in a “tail spin” and desperate for information that might lengthen survival time or better yet, make mesothelioma into a chronic disease. It is crucial that time is taken to consider all of the options in a calm, supportive environment to ensure that decision making is optimized.

I outlined below some very promising new clinical trials. PLEASE NOTE: This is not a comprehensive list of available trials. Each mesothelioma case is different, so please only use this list as a loose guide. To obtain a full consultation, which will take into consideration all available treatments, please contact Mary Hesdorffer, APRN.

Among treatment options available today are specialized forms of radiation therapy given before or following a surgical procedure. Recently, a small trial using IMRT (Intensity-Modulated Radiation Therapy) prior to an extrapleural pneumonectory (EPP) demonstrated a 50% increase in survival over historical controls. A randomized trial is now in the planning stages to confirm these results in a larger patient population.

There are other trials currently under IRB review that will look at IMRT following either an EPP or Pleurectomy Decortication (PD). Randomized trials are the only way for scientists to demonstrate whether an intervention is better than the standard of care.

In fact, a randomized trial of a PD vs. PD, coupled with photodynamic therapy (PDT) has recently commenced following an initial, single center, non-randomized trial, which reported a significant increase in overall survival, including patients with advanced disease.

Another trial I’d like to mention uses a vaccine (CRS207) prior to treatment with Alimta and Cisplatin. It has reported a 69% durable response. A larger trial is now underway to confirm these results with plans for a future randomized trial.

Patients who respond or are stable following treatment with Alimta and Cisplatin are also eligible for Defactinib, an agent targeting cancer stem cells with the goal of lengthening the time to relapse or perhaps, in the best case scenario, preventing relapse altogether.

In the second-line setting (for patients who have had a recurrence following first-line treatment), immunotherapy appears to have taken the lead with a multi-nation, placebo-controlled trial of the drug tremelimumab. In melanoma, this agent has induced durable responses and, so far, has shown much promise in mesothelioma.

Definitely worth mentioning is also the NCI’s stellar new drug SS1P, an immunotoxin which utilizes mesothelin (a protein) to gain entry into the cell. Early phase I studies have demonstrated results in advanced patients who had failed multiple prior treatments, and a phase II study is currently underway.

These are just a few of the trials currently offered to mesothelioma patients. We strongly urge clinicians to refer patients to clinical trials in mesothelioma, as they are known to expedite research progress.

For instance, children’s cancers that saw the highest enrollment in clinical trials have experienced significant advances in treatments of those conditions. Our hope is to do the same for mesothelioma.

Visit curemeso.org to view the Meso Foundation’s Clinical Trials Brochure and learn more about enrolling in a clinical trial.

Summary of Mesothelioma Studies Presented at ASCO

Microscopeby Lee M. Krug, MD, Memorial Sloan Kettering Cancer Center

The American Society of Clinical Oncology meeting was held from May 30 – June 3, 2014 in Chicago. This is the largest oncology meeting each year with around 30,000 attendees from all over the globe who congregate to discuss the latest research in all cancer types. I will provide you with my annual summary of the most prominent studies in mesothelioma.

Randomized trial of arginine deprivation with ADI-PEG20: This abstract was presented by Dr. Szlosarek from the United Kingdom. Arginine is an amino acid that normal cells make using an enzyme called ASS (time to make the joke here!). However, many cancer cells lack the ASS enzyme so they cannot make arginine and they need to get it from outside the cell. ADI-PEG20 starves the cancer cells of arginine. In this trial, patients with mesothelioma were randomized to receive treatment with ADI-PEG20 or just supportive care. In order to qualify, the tumor samples were tested to make sure they had low levels of ASS. Side effects were very mild with this treatment. About half of the patients had stabilization of their disease. The time for cancer growth to occur was longer in the ADI-PEG20 arm, but only by a small margin (1.9 versus 3.2 months). A future study will combine ADI-PEG20 with chemotherapy, and that trial should open later this year.

Phase 2 study with tremelimumab: Probably the hottest drugs in oncology right now are the antibodies that boost the immune system. These types of treatment have shown great benefit in melanoma, lung cancer, and many others. Tremelimumab is one of these drugs, and this trial, conducted in Italy by Dr. Calabro and colleagues, showed that mesothelioma also responds to these therapies. Of the 29 patients, 14% of patients had shrinkage of their mesothelioma and 38% had stabilization. These data support the international, randomized trial with tremelimumab that is currently ongoing that will include 542 patients. If this large trial shows that tremelimumab improves survival, this drug will get FDA approval for mesothelioma.

Anti-mesothelin vaccine CRS-207 plus chemotherapy: Dr. Hassan from the National Cancer Institute reported these results. Mesothelin is a protein on the surface of mesothelioma tumors, and seems to be an excellent target for treatment. CRS-207 is a vaccine that increases the immune response against mesothelin. In this study, CRS-207 was given with pemetrexed and cisplatin. Nearly 70% of patients had shrinkage of their cancer, much more than usual with chemotherapy alone, and the responses seemed to last longer. These results should encourage a larger future randomized study.

Next-generation sequencing in mesothelioma: The report from Dr. Scagliotti at the University of Turin, Italy, described his findings from an analysis of gene mutations in a group of mesothelioma tumor samples. This type of testing has become critical for identifying potential targets in all cancers, and customizing treatment for each patient.


Lee M. Krug, MD, is an Associate Attending Physician in the Division of Thoracic Oncology, Department of Medicine at Memorial Sloan-Kettering Cancer Center in New York, New York, where he completed a fellowship and chief fellowship in medical oncology. Dr. Krug is the Director of the Mesothelioma Program at Memorial Sloan-Kettering Cancer Center. He is also the chair of the board of directors of the Meso Foundation.

Update on Mesothelioma: A CancerCare Teleconference

CancerCare Update on MesotheliomaOn Monday, June 30 from 4:30-5:30PM Eastern Time, CancerCare is hosting a free mesothelioma teleconference workshop. The teleconference, titled Update on Mesothelioma, will feature a panel of experts to discuss numerous topics related to the disease. Registrants will be able to listen in on the phone or through a live stream online.

The Update on Mesothelioma teleconference will cover topics including mesothelioma treatment choices; the role of clinical trials; managing side effects, discomfort and pain; communicating with your health care team; quality of life and life style concerns; and physical activity and nutrition issues and tips. Questions for the panel of experts will also be accepted.

The panel of experts consists of four individuals: Richard J. Gralla, MD, FACP, Professor of Medicine, Albert Einstein College of Medicine; Lee M. Krug, MD, Director of the Mesothelioma Program, Associate Attending Physician, Division of Thoracic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Mary Hesdorffer, MS, APRN-BC, Nurse Practitioner, Executive Director, Mesothelioma Applied Research Foundation; and Winfield Boerckel, MSW, MBA, Director of Social Service – Long Island, Lung Cancer Program Coordinator, CancerCare.

Mary Hesdorffer, MS, APRN-BC, is an expert nurse practitioner with over 16 years of experience in mesothelioma treatment and dozens of published articles in a variety of scientific journals. She is the executive director of the Meso Foundation and the first line of help for patients and caregivers faced with a mesothelioma diagnosis.

Lee M. Krug, MD, is an Associate Attending Physician in the Division of Thoracic Oncology, Department of Medicine at Memorial Sloan-Kettering Cancer Center in New York, New York, where he completed a fellowship and chief fellowship in medical oncology. Dr. Krug is the Director of the Mesothelioma Program at Memorial Sloan-Kettering Cancer Center. He is also the chair of the board of directors of the Meso Foundation.

To register for the free Update on Mesothelioma teleconference workshop, visit CancerCare.org.

Meet the Experts: Dr. Valerie Rusch, Memorial Sloan-Kettering Cancer Center

Meet the Experts: Dr. Valerie Rusch

The Meso Foundation would like to invite you to join us for the next installment of our Meet the Experts series: “Focused Discussion on a New Clinical Trial: GL-ONC1” on Monday, February 17 at 8 PM Eastern Time, featuring Dr. Valerie Rusch, Memorial Sloan-Kettering Cancer Center.

The teleconference will follow our usual format with Mary Hesdorffer, Nurse Practitioner, as the moderator. We encourage all listeners to submit questions through our Facebook page and email throughout the call.

The teleconference is free, but does require that you RSVP in order to receive the call-in information. You can RSVP here.

Dr. Valerie Rusch of the Memorial Sloan-Kettering Cancer Center is a thoracic surgeon with over 25 years of experience. Her focus is treatment of patients with cancers of the lung, airways (trachea, bronchi), esophagus, mediastinum, chest wall, and pleura (malignant pleural mesothelioma). Read more about Dr. Rusch here.

You can listen to previous Meet the Experts sessions, including our most recent session, “New Frontiers in Surgery” with Dr. Joseph Friedberg, on our Meet the Experts page.

The Anatomy of Clinical Trials for Mesothelioma

Recently, we had the honor to interview Melissa Culligan, RN, BSN, MS, a thoracic surgery nurse with specialized experience designing clinical trials. To listen press PLAY in the above podcast box (it may take a minute for the podcast to load).

In a cancer like mesothelioma, for which there is only one FDA-approved treatment, clinical trials play an integral role in many patients’ treatment regimens. For this reason, we wanted to provide patients with a solid overview of clinical trials, their design, and implementation.

Melissa Culligan with Dr. Friedberg, Karen Mudrick, and Mary Hesdorffer at Meso Foundation's 2013 Symposium.

Melissa Culligan with Dr. Friedberg, Karen Mudrick, and Mary Hesdorffer at Meso Foundation’s 2013 Symposium.

Melissa Culligan, RN, BSN, MS has worked as a thoracic surgery nurse for over 25 years and has worked in the field of thoracic oncology research for the past 15 years. She currently works in the Division of Thoracic Surgery at Penn-Presbyterian Medical Center and is the Director of Clinical Services for the Penn Mesothelioma and Pleural Program. She has a special interest in the areas of mesothelioma and advanced stage lung cancer and has recently graduated from Drexel University’s School of Medicine’s Master’s Program in Clinical Research Organization and Management.

Are you interested in learning more about clinical trials for mesothelioma? Do you have questions about mesothelioma clinical trials? Talk to our mesothelioma specialists through our Ask the Expert feature now.