A Summary of Mesothelioma Studies from ASCO 2015

MicroscopeBy Hedy Lee Kindler, MD,  University of Chicago

The American Society of Clinical Oncology meeting was held from May 29 – June 2, 2015 in Chicago. About 30,000 attendees from across the world gathered to discuss the latest research advances in all types of cancer, making this the largest, most important oncology meeting of the year. This was a particularly exciting meeting for those of us interested in mesothelioma. I’ve summarized 3 of the most prominent studies below.

MAPS: A randomized trial of pemetrexed, cisplatin with or without bevacizumab. This oral abstract, presented by Dr. Gerard Zalcman on behalf of the French Cooperative Thoracic Intergroup (IFCT), was clearly the star of the show for those of us who care about mesothelioma. This study is important because it is the first randomized trial in over a decade to show that a new drug improves survival in mesothelioma patients. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), which is highly expressed on mesothelioma. Think of it as a drug that targets the blood vessels that feed tumors (angiogenesis). Bevacizumab (the trade name is Avastin) is already FDA approved in multiple cancers, including colon cancer and lung cancer. In the MAPS trial, all 448 patients received standard chemotherapy with pemetrexed plus cisplatin, and half of the patients were randomized to also receive bevacizumab with each dose of chemotherapy. After completing 6 cycles of chemotherapy, patients on the bevacizumab arm also received bevacizumab by itself, every 3 weeks until their cancer started to grow. The time for cancer growth to occur (progression-free survival) was about 2 months longer in the bevacizumab arm (9.59 vs. 7.48 months). Patients treated with bevacizumab also lived almost 3 months longer (18.82 vs. 16.07 months). The addition of bevacizumab did not make patients feel worse (it did not worsen quality of life), although it did cause increased side effects such as bleeding, high blood pressure, and blood clots. Because there was an improvement in survival with the experimental treatment, it is possible that this trial could lead to FDA approval of bevacizumab for mesothelioma—stay tuned!

NGR015: Randomized trial of investigator’s choice of chemotherapy with or without NGR-hTNF. Oral presentations at ASCO are only for the large randomized trials. At most ASCO meetings there are no mesothelioma presentations; this year, there were two! The second oral presentation was by Dr. Rabab Gaafar from Cairo, Egypt on behalf of an international group of investigators. All 400 patients on this trial previously received pemetrexed. They were randomized to receive either NGR-hTNF (another drug that targets angiogenesis) or placebo (sugar water).  In addition, patients could receive chemotherapy either with gemcitabine, vinorelbine, or doxorubicin, or no chemotherapy at all. Unfortunately, the addition of NGR-hTNF to chemotherapy did not affect how long the cancer was controlled, or how long the patients lived. Data is being analyzed to see if certain characteristics might predict which patients might benefit from this drug.

Mesothelin targeted immunotherapy CRS-207, plus pemetrexed/cisplatin chemotherapy. Dr. Raffit Hassan from the National Cancer Institute updated the results of this ongoing trial in a poster presentation. Mesothelin is highly expressed on the surface of mesothelioma. CRS-207 is a vaccine that increases the immune response against mesothelin, and may enhance the activity of chemotherapy. In this study, 2 doses of CRS-207 were given before pemetrexed and cisplatin, as well as after completion of 6 cycles of chemotherapy. Encouraging activity was observed: 60% of patients had tumor shrinkage, and another 34% had disease that did not grow. Thus 94% of patients had disease that was controlled with this experimental vaccine plus chemotherapy. This is much better than would be expected with chemotherapy by itself. Based on these encouraging results, a randomized study to test this combination compared with standard chemotherapy is in development.

Hedy Lee Kindler, MD, an internationally recognized authority on the treatment of mesothelioma, is a Professor of Medicine and the Director of the Mesothelioma and Gastrointestinal Oncology Programs at the University of Chicago. Dr. Kindler is a Past President of the International Mesothelioma Interest Group. She was a member of the Science Advisory Board of the Mesothelioma Applied Research Foundation from 2001-2014, and remains active with the Foundation.  Dr. Kindler chairs the Mesothelioma Subcommittee of the Alliance for Clinical Trials in Oncology, a national cancer clinical trials group. Her research focuses on the investigation of novel agents for the treatment of mesothelioma. Patients from throughout the United States come to Dr. Kindler’s Mesothelioma Clinic at the University of Chicago for her expert care and to participate in her many clinical trials. Dr. Kindler has been listed repeatedly in Best Doctors in America, America’s Top Physicians, America’s Top Doctors for Cancer, and Best Doctors in Chicago.

Updates from ASCO: CRS-207 Vaccine Study Results

MicroscopeAduro BioTech is conducting a clinical trial to test an investigational new immunotherapy for malignant pleural mesothelioma (MPM). This therapy, called CRS-207, is given to a patient in combination with chemotherapy in hopes of encouraging the body’s normal defense mechanisms to fight off the cancer. This trial aims to enroll up to 60 patients at 5 U.S. clinical sites. The company presented data at the American Society of Clinical Oncology (ASCO) conference this week showing that of the 32 patients with MPM treated with CRS-207 and chemotherapy, MPM tumors reduced in size for 19 patients, and tumors remained the same size (stable) in an additional 11 patients. CRS-207 is given prior to and after chemotherapy (cyclophosphamide, pemetrexed and cisplatin) for patients who have not received prior treatment or surgery for their disease.

If you are interested in participating in a clinical trial for this investigational new therapy, please click here.

The 2015 ASCO Annual Meeting, one of the largest oncology meetings of the year, was held from May 29 to June 2 in Chicago, Illinois. The Meso Foundation will be providing more information on studies presented at ASCO in the coming weeks.

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.