A Summary of Mesothelioma Studies from ASCO 2015

Microscope

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.

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