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.

Mark Your Calendar for Upcoming Mesothelioma Conferences

2013 International Symposium on Malignant MesotheliomaThis year, the Meso Foundation will be host to two regional conferences. The first will be held on Friday, September 26 at the University of Pennsylvania in Philadelphia, Pennsylvania. The second will be held on Friday, October 10 at the University of Chicago in Illinois. Each conference will feature regional experts in the field of mesothelioma. Check back to curemeso.org for further information as it becomes available or sign up for our e-news to ensure you are notified as conference details are released.

September 26, 2014
University of Pennsylvania
The Hub, Cira Centre
2929 Arch Street
Philadelphia, PA 19104

October 10, 2014
University of Chicago
Palmer House Hilton
17 E Monroe Street
Chicago, IL 60603

Annual Conference
The Meso Foundation’s annual conference, the International Symposium on Malignant Mesothelioma, along with the Scientific Seminar, will be held from Monday, March 2 through Wednesday, March 4, 2015 in partnership with the National Cancer Institute in Bethesda, Maryland. Events will be held at the National Institutes of Health Natcher Conference Center and the Hyatt Regency Bethesda. Symposium registration will open on October, 13, so mark your calendars now! Visit curemeso.org/symposium for more information as it becomes available or sign up for our e-news to be notified about Symposium details.

International Symposium
on Malignant Mesothelioma
March 2- 4, 2015
National Institutes of Health
Natcher Conference Center (Building 45)
Bethesda, MD
Hyatt Regency Bethesda
7400 Wisconsin Ave
Bethesda, MD 20814

Scientific Seminar
March 2-3, 2015
National Institutes of Health
Natcher Conference Center (Building 45)
Bethesda, MD

 

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.

Looking for Inspiration

Running on treadmillby Mary Hesdorffer, NP, Executive Director of the Meso Foundation

I found myself on the treadmill looking for inspiration to go the extra mile. Two miles into it and I am running out of steam. I am not an ESPN fan, which means that I have to take inspiration from another source. Into my mind pops up the image of Joe Friedberg, MD.

Of course, I wonder, who else would channel Joe Friedberg while on a treadmill? Am I losing it?

As you know, Joe is a champion in the field of mesothelioma, toughing it out in the operating room with a grueling procedure, which has recently reported some promising results. I recalled a conversation with Joe when he suggested that to complete a pleurectomy decortication, one has to be totally committed to going the extra mile (as these operations last up to 8 hours) and one has to be willing to persevere through fatigue, and physical and mental challenges.

There has been much debate about surgery – extrapleural pneumonectomy (EPP) vs. pleurectomy decortication (PD) vs. those who believe that surgery should not be offered to patients with mesothelioma, and advocate for palliative care only.

I think about Joe in these debates, and his honesty and lack of bravado when he simply states that “we don’t know what is the best surgical option to offer patients and that all surgery in this disease is experimental.” Though the uncertainty is unsettling, the honesty is refreshing.

Recently, Dr. Friedberg and his team at UPENN have launched a new clinical trial that will randomize patients to either a pleurectomy decortication or a pleurectomy decortication coupled with photodynamic therapy. Joe has spent many years championing photodynamic therapy as an adjuvant therapy to his pleurectomy decortication surgery, making this clinical trial a one-of-a-kind move to get closer to the truth.

Doing 3 miles on a treadmill no longer seems daunting.

Here is why Joe’s courage is so important and why I hope others follow in his footsteps. It is well-known among researchers that most surgical studies have an inherent bias to them. In other words, a surgeon’s excellent numbers may be produced not only by their skill, but also by choosing to operate on patients who have the best chance to tolerate the surgery and do well after. The fact is, surgery often results in a surgical remission, but unfortunately, in mesothelioma, the cancer generally returns after a certain period of time. To extend the remission, surgeons use specific adjuvant therapies to lengthen the time to progression and, of course, create the best case scenario to prevent the return of disease. This is the crux of the discussion about what will kill the cells that are waiting like seeds in a garden ready to sprout into recurrent disease.

I am appalled to hear so many surgeons in this disease state quite frankly that their approach works and there is no need to do a randomized trial which will eliminate bias from their results. Worse yet are those surgeons who boast that their patients do better in their hands, with their procedure yet when I scour the literature there are no published reports in scientific journals. In academic medicine there is a phrase “If it isn’t published, it never happened.” In other words it is expected that you submit your results to a peer reviewed journal to demonstrate that your outcomes are accepted by your peers and your data has been analyzed by, and scrutinized by unbiased reviewers who are experts in the field of surgery. There is no room for arrogance when we are losing patients in these procedures. We need to know what is the true statistical difference. The gold standard is to compare a new hypothesis and test it against the standard to see if this really is a significant improvement.

Dr. Friedberg has reported some impressive results with his combination of pleurectomy decortication combined with photodynamic therapy, and now he’s willing to take a step further to understand if there is a difference between patients undergoing pleurectomy decortication alone from those getting both the surgery and the adjuvant therapy.

This is what the mesothelioma community needs – “proof of the pudding.” We truly do not know what is better so we need to strip back the notion of “my treatment works, and I don’t need to prove it.” Randomized clinical trials can help us find a gold standard of treatment for mesothelioma.

I guess, what that means is that I, too, should be going the extra mile on this treadmill. Mile 4, here I come.

Meso Foundation Updates its Peer-Review for Research Grant Funding

ResearchAs the only non-government funder of peer-reviewed mesothelioma research, the Meso Foundation has announced an update to its peer-review process for evaluating research grant proposals, so as to once again match the process by the National Institutes of Health (NIH).

The Foundation has always modeled its peer-review process after the NIH, so when the NIH made changes in 2013, the Foundation followed suit.

The change involves streamlining the reviews by eliminating the two-step process and replacing it with one step only. Instead of sending a project through two separate rounds of review, which would usually result in a total of 3-4 number of reviewers looking at each project, now all 3-4 reviewers evaluate the project in the one and only round. This ensures a quicker review turnaround and a more efficient process.

To learn more about the Meso Foundation’s research grant program, visit curemeso.org.