Summary of Mesothelioma Studies Presented at ASCO

Lee M. Krug, MD shares his annual summary of the mesothelioma research presented at the American Society of Clinical Oncology (ASCO) meeting.by 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.

Review: Report on Mesothelioma

mapby Mary Hesdorffer, Nurse Practitioner
Executive Director, Mesothelioma Applied Research Foundation

Researchers from Creighton University School of Medicine accessed the National Cancer Database (NCD), and issued a report on their findings. They analyzed the years between 2000 and 2010. In the United States, 26,605 patients were diagnosed during this period of time. The NCD accumulates this data on approximately 70% of all cancers diagnosed in the states. If one were to add in the 30% not recorded it would take us close to the number of 3,458 cases per year that we use as a figure when we present on mesothelioma.  This supports that the numbers of diagnosed mesothelioma patients have remained fairly steady over these past years.

Not surprising were the reports that mesothelioma patients were 89% Caucasian, 78% male and 60% over the age of 70. We talk about the changing face of mesothelioma, but perhaps that perception is created because younger patients access the web, engage in social media and are able to draw more attention to their plight. Or perhaps one could argue that when 30% remain unaccounted for in this database the figures could be different in terms of age, race and gender.

Recently, I took the opportunity to speak with Dr. Karen Antman, Dean of Boston University School of Medicine, to discuss the earliest days of mesothelioma research. Dr. Antman, prior to writing one of the first clinical trials in mesothelioma, canvased the database of the Harvard system and told me that even then she was surprised by the number of young patients she found in the archives. So perhaps this phenomenon is not new.

What does not surprise me is that 36% of patients under the age of 50 underwent surgery, and 12% over the age of 80 also underwent a surgical procedure. It takes a good physicality to undergo this surgery and return to a quality of life that is sustainable and acceptable to the majority of patients.

In reading the report, what did not surprise but disgusted me, was that insurance weighed so heavily in the surgical arena. “Patients with private insurance received more surgical treatment (28%) than patients with Medicaid (22%), Medicare (18%), and VHA (12%)(p<0.009)” (J Clin Oncol 31, 2013 (suppl; abstr e18501). Our Veterans seem to be denied surgery when compared to those with private insurance.  21% of all patients in this database underwent surgery which explains why attempting to mount a robust surgical trial in mesothelioma will not be possible and we will continue to rely on case series and small powered trials to obtain surgical statistics in advising our patients.

Want to learn more about mesothelioma research? Ask one of our experts.

Update from The American Society of Clinical Oncology (ASCO) Annual Meeting

By Lee Krug, MD, Memorial Sloan-Kettering Cancer Center

ASCO-2013_1The American Society of Clinical Oncology meeting was held from June 1-4 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 thought I would summarize a few of the presentations that were made regarding mesothelioma.

Accelerated hypofractionated hemithoracic intensity modulated radiation therapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma (IMRT)

This study was presented by Dr. Marc de Perrot from Toronto, a member of our Science Advisory Board. In this approach, patients with early stage mesothelioma are treated first with high dose radiation over one week, and then, after one week of rest, patients then undergo an extrapleural pneumonectomy (EPP). If patients were found to have mediastinal lymph nodes at the time of surgery, they were planned to get chemotherapy afterward. This was a select group of patients who participated since only 18% of the patients with mesothelioma seen at the center over 4 years were enrolled on this study. Amazingly, the complications after the surgery were not more than expected, though one patient did die of an infection. Furthermore, the survival rates were quite promising; for patients with epithelioid subtype, 85% were predicted to be alive after 3 years. This is a high risk, aggressive treatment modality appropriate for only a select group of patients, and more follow up is needed. However, the excellent survival results are notable.

Randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma

This was a trial conducted at a single institution in the Netherlands.  The researchers were aiming to find a drug that would improve the results of standard Pemetrexed (Alimta) and cisplatin chemotherapy. In this study, another drug called axitinib was added to that chemotherapy combination. Axitinib is an oral drug that blocks the vascular endothelial growth factor receptor (VEGFR) which is responsible for the formation of new blood supply to feed the tumor, which contributes to tumor growth. Patients were placed in two groups, one-third receiving treatment with pemetrexed and cisplatin alone, and two-thirds receiving the same chemotherapy plus axitinib. Patients received three cycle of therapy, and then underwent a pleurectomy (PD). The rate of tumor shrinkage and survival times were no different with the addition of axitinib, but the trial was quite small with only 31 patients in total, so it is difficult to draw definitive conclusions.

Phase I study of cediranib in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma

Dr. Anne Tsao from MD Anderson (another member of our Science Advisory Board) presented the results of this study on behalf of the Southwest Oncology Group. This study had a similar goal, to find a drug that could be added to standard chemotherapy. Like axitinib, cederinib is a pill that blocks the VEGF receptor, but it also blocks another growth factor called platelet derived growth factor receptor (PDGFR).  This study was designed to determine the side effects of that treatment and find the best dose. Twenty patients received the combination, and two doses of cederinib were tested. Patients received 6 rounds of chemotherapy plus cederinib, and then stayed on cederinib as a maintenance therapy after that. At the higher dose, two patients had severe diarrhea, two had debilitating fatigue, and one had confusion, so the lower dose was chosen for further study. Although the number of patients with tumor shrinkage was not impressive, the time before the cancer grew again was much longer than usual. A larger study is now ongoing in which patients are randomized, some receiving chemotherapy alone and some with chemotherapy plus cederinib.

Sensitivity of malignant mesothelioma lacking Merlin to the FAK inhibitor VS-6063: Evaluation of merlin/NF2 status in clinical samples

One of the genes that is commonly mutated in mesothelioma tumors is NF2 “(neurofibromin 2) This gene makes a protein called Merlin. Merlin sends growth signals inside the cancer cell and one of the proteins it interacts with is focal adhesion kinase (FAK). This abstract reported on experiments in the laboratory. The researchers treated mesothelioma cancer cells and also tumors in mice with a drug that blocks FAK called VS-6063. The treatment worked best in tumor cells that had NF2 mutations supporting their hypothesis. They have used this information to plan a large randomized trial with VS-6063 that is set to start this summer. Patients who have completed initial treatment with chemotherapy will be randomized to receive VS-6063 or placebo, to see if this drug delays the time before the cancer will start to grow again.

FROM THE MESOTHELIOMA APPLIED RESEARCH FOUNDATION’S “MEET THE EXPERTS” SERIES: Introducing a New Clinical Trial with Dr. Julie Brahmer

Tonight, as part of the “Meet the Experts” podcasts presented exclusively by the Meso Foundation, Dr. Julie Brahmer, Associate Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, sat down with Mary Hesdorffer, Nurse Practitioner and Medical Liaison for the Meso Foundation, to discuss her new trial targeting pleural mesothelioma. In her talk “NGR-hTTNF: A New Multi-Center Drug Trial for Pleural Mesothelioma”, Dr. Brahmer discussed a new chemotherapy treatment, designed specifically for pleural mesothelioma patients.

To participate in the trial, one prior treatment regimen is required (for example Alimta and Cisplatin) which usually consists of 4 to 6 treatments. The NGR-hTTNF trial can then be offered in the second line setting. Patients will receive an active chemotherapy agent, and plus or minus the experimental drug NGR-hTTNF. This trial is available worldwide. In the United States, it can be obtained at Johns Hopkins in Baltimore, Maryland, as well as a few others sites in Texas, California, and New York. According to Dr. Brahmer, it consists of a weekly treatment, with the most common side effects resulting in fatigue, nausea, headaches, and generalized weakness. The enrollment process into the NGR-hTTNF trial begins with an appointment with an investigator in trial.

The investigator reviews whether or not the patient is eligible based on treatments already received, the patient’s stage of mesothelioma, and his or her general physical well-being. Following this appointment, the patient must sign the consent form, after which eligibility is finalized through a few additional tests. If patients have responded positively or remain stable, chemotherapy will be discontinued after six cycles and patients will be extended an opportunity to receive NGR-hTTNF as a maintenance therapy. The primary end point of this trial will be to extend survival rates with secondary endpoints of improving quality of life and diminished symptoms of mesothelioma.

Having just returned from the annual Annual Meeting of the American Society for Clinical Oncology (ASCO) conference in Chicago, IL, where another expert from our “Meet the Experts” series — Dr. Lee M. Krug — gave his own summary of the event, Dr. Brahmer feels optimistic and excited about possibilities ahead. “I think a lot of the things we’re learning in lung cancer research may affect patients with mesothelioma,” she states. “There are some therapies being developed that stimulate the immune system, and I hope those types of drugs will have some type of role in combatting mesothelioma, as well.”

Dr. Brahmer’s research and clinical practice focuses on the development of new therapies for the treatment and prevention of lung cancer and mesothelioma. Dr. Brahmer has published several papers in this area of research and is a member of the American Society of Clinical Oncology and the Eastern Cooperative Oncology Group (ECOG) Thoracic Committee and Cancer Prevention Steering Committee. She is one of the founding Board members for the National Lung Cancer Partnership (formerly Women Against Lung Cancer). Within the National Lung Cancer Partnership she currently serves as a member and the Chairman of the Scientific Executive Committee. She serves on the medical advisory board of the Lung Cancer Research Fund and is a former member of the Mesothelioma Applied Research Foundation’s Science Advisory Board.

More information about this trial is available at the Meso Foundation by emailing mary@curemeso.org or by calling (703) 879-3820. If you missed tonight’s “Meet the Experts” presentation, you can replay Dr. Brahmer’s talk and find out more about our other mesothelioma research resources at curemeso.org.

GUEST POST: An ASCO Update from Dr. Lee M. Krug, MD

The Meso Foundation is happy to present this special guest blogpost from Lee M. Krug, MD, Associate Attending Physician in the Division of Thoracic Oncology, Department of Medicine at Memorial Sloan-Kettering Cancer Center in New York, New York and Director of the Mesothelioma Program at Memorial Sloan-Kettering Cancer Center. Dr. Krug has investigated multimodality approaches for patients with early stage malignant pleural mesothelioma, has led a multicenter U.S. trial of induction chemotherapy before extrapleural pneumonectomy, and has a current study testing the feasibility of chemotherapy followed by pleural radiation. Dr. Krug also has a strong interest in novel therapeutics for patients with more advanced disease, and is the principal investigator of an international, phase III trial of a histone deacetylase inhibitor, vorinostat. Dr. Krug led the committee for the National Comprehensive Cancer Network (NCCN) that established treatment guidelines for mesothelioma, and is currently the chairman of the Scientific Advisory Board and serves on the Board of Directors at the Meso Foundation.

The Annual Meeting of the American Society for Clinical Oncology (ASCO) was held in Chicago, IL from June 1-5, 2012. This is the largest meeting in oncology each year with over 25,000 attendees from all over the world. Several abstracts of interest to mesothelioma were presented, so I thought I would summarize the results of a few of the most interesting:

Randomized Phase II Trial of Pemetrexed/Cisplatin with or without CBP501 in Patients with Advanced Malignant Pleural Mesothelioma: CBP501 is a novel compound that enhances the ability of cisplatin to damage cancer cells. In this international trial, patients received treatment with standard chemotherapy (pemetrexed and cisplatin), or they received it in combination with CBP501. 63 patients participated in total; 40 were in the group with CBP501. The only additional side effect of CBP501 seemed to be a rash that occurred during the infusion. Forty percent of the patients who received chemotherapy plus CBP501 had tumor shrinkage as compared to 17% of the patients who received chemotherapy alone. The average time before the cancer grew back was 5.9 months in the CBP501 arm, and 4.7 months in the other arm. Although the patients who received chemotherapy alone fared less well than expected, the results seemed encouraging. Another similar trial with CBP501 has also been conducted in lung cancer and until those results become available later this year, plans for future trials are unclear. Continue reading “GUEST POST: An ASCO Update from Dr. Lee M. Krug, MD” »