“Genetically modified versions of patients’ own immune cells successfully traveled to tumors they were designed to attack in an early-stage trial for mesothelioma and pancreatic and ovarian cancers at the Perelman School of Medicine at the University of Pennsylvania. The data adds to a growing body of research showing the promise of CAR T cell technology. The interim results will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2015, April 18-22.
” ‘The goal of this phase I trial was to study the safety and feasibility of CART-meso cells in patients with mesothelin-expressing tumors,’ says Janos L. Tanyi, MD, PhD, an assistant professor of Gynecologic Oncology. ‘We found no major adverse events associated with the treatment, which suggests that the patients tolerated it very well. But importantly, the T cells successfully targeted the patients’ tumor sites and survived in the blood stream for up to 28 days.’
“Tanyi will present data on five patients (two with ovarian cancer, two with epithelial mesothelioma, and one with pancreatic cancer) who received the new investigational therapy. All patients who received the therapy had cancers which had stopped responding to conventional treatments.”
“One of the hot new cancer immunotherapy drugs, Merck & Co.’s Keytruda, strongly benefited patients with melanoma, lung cancer and mesothelioma, according to three studies presented Sunday at the American Association for Cancer Research conference in Philadelphia.
“One study, comparing Keytruda to Bristol-Myers Squibb Co.’s Yervoy, could give Merck a temporary advantage as the rivals battle for market supremacy and billions of dollars in annual sales from this new generation of drugs, which help the immune system destroy cancer cells. While research continues, the pace is quickening and big improvements in patient care regimens are likely fairly soon.”
“The PD-1 inhibitor pembrolizumab, a cancer immunotherapy drug, shrank or halted growth of tumors in 76 percent of patients with pleural mesothelioma, a rare and deadly form of cancer that arises in the outer lining of the lungs and internal chest wall, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania. Patients diagnosed with the disease, which is tied to exposure to asbestos, have a median survival rate of about one year.
“The findings will be presented on Sunday at the 2015 American Association for Cancer Research (AACR) Annual Meeting, being held in Philadelphia April 18-22.
“An international team of scientists from the United States, Europe, and the United Kingdom led by Evan W. Alley, MD, PhD, co-director of the Penn Mesothelioma and Pleural Program, found that of 25 patients administered the medication, seven (28 percent) experienced tumor shrinkage and the drug appeared to halt tumor growth in 12 patients (48 percent) . Four patients (16 percent) had disease that progressed, and two patients had not been assessed at the time of analysis. No patients discontinued treatment because of serious drug-related adverse events.
” ‘The 76 percent disease control rate in this set of patients previously treated for malignant pleural mesothelioma is very promising and represents a signal of efficacy in the treatment of this disease,’ said Alley. ‘Our team was also gratified that none of our patients had unexpected side effects, there were no patient deaths related to the treatment, and we managed all adverse events without discontinuing treatment.’ “
“AstraZeneca today announced that the US Food and Drug Administration has granted Orphan Drug Designation for the anti-CTLA-4 monoclonal antibody, tremelimumab, for the treatment of malignant mesothelioma.
“Mesothelioma is a rare, aggressive cancer that most often affects the lining of the lungs and abdomen. Available treatments for mesothelioma are very limited, particularly for patients with advanced disease.
“ ‘There is a significant need for new treatment options for patients with mesothelioma because fewer than five percent of patients currently survive beyond five years, even when they receive timely diagnosis and care. Our aim is to rapidly advance the development of tremelimumab as a potential new treatment option for these patients,’ said Robert Iannone, Senior Vice President, Head of Immuno-oncology, Global Medicines Development at AstraZeneca.
“The Orphan Drug Designation programme provides orphan status to drugs and biologics, which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US1.”
The gist: The U.S. Food and Drug Administration (FDA) has granted “orphan drug” designation to a new drug called vs-5584 (Verastem) for mesothelioma. The designation will make it easier for the drug maker to successfully develop Verastem and get it to patients in the U.S. Verastem has shown promise in patients in a clinical trial.
“The FDA granted orphan drug designation to VS-5584 for the treatment of mesothelioma, according to a press release from the drug’s manufacturer.
“VS-5584 (Verastem) has demonstrated potent and highly selective activity against class 1 PI3K enzymes and dual inhibitory actions against mTORC1 and mTORC2, according to a press release issued by Verastem.
“ ‘This is an important regulatory milestone for Verastem and, together with our European orphan medicinal product designation, will facilitate our global development of VS-5584 to help improve the available treatment options for patients suffering from this highly aggressive cancer,’ Robert Forrester, president and CEO of Verastem, said in a press release. ‘We look forward to taking full advantage of the opportunities that orphan designation allows in order to bring this potential new treatment option to patients as rapidly as possible.’ ”
The gist: This article discusses new findings for mesothelioma treatment from two research studies. The first study was a clinical trial—a research study with volunteer patients. The researchers found that people with malignant pleural mesothelioma who have been treated with chemotherapy and surgery unfortunately do NOT benefit from further treatment with high-dose radiation therapy. The second study was more promising. It found that 20% of people with malignant pleural mesothelioma have cancer cells that express the immune system protein PD-L1. This is important because immunotherapy drugs have already been developed to fight cancers that express PD-L1, such as other forms of lung cancer and melanoma. Clinical trials may soon test whether mesothelioma patients could benefit from anti-PD-L1 drugs.
“Treating patients with high-dose radiotherapy after chemotherapy and surgery for malignant pleural mesothelioma does not achieve improvements in local relapse and overall survival, according to data from a prospective randomized phase II trial presented at ESMO 2014 Congress in Madrid.
” ‘Mesothelioma remains a difficult disease to find better treatment options for, so we asked whether high-dose hemithoracic radiotherapy would decrease the rate or delay the time of local recurrence after chemotherapy and radical surgery,’ says lead author Prof Rolf A. Stahel, from the Clinic and Policlinic for Oncology, at the University Hospital Zurich, Switzerland, and current President of the European Society for Medical Oncology.
“The multicentre trial included 153 patients with surgically-treatable malignant pleural mesothelioma, who were first treated with three chemotherapy cycles of cisplatin and pemetrexed, followed by surgical removal of affected lung tissue, with the goal of complete removal of the cancerous areas of lung.”
The gist: Some patients with cancer in the chest (such as lung cancer and mesothelioma) are treated with high-dose thoracic radiation therapy. The effects of this treatment are not well-known. Researchers recently looked into the effects of high-dose thoracic radiation therapy on patients’ hearts. They found small effects just after treatment, but these effects disappeared 1-2 months later. The researchers say further research needs to be done to better understand the short- and long-term effects.
“There were only modest acute changes in cardiac biomarkers and electrocardiograms and there were no clinically significant cardiac events in patients with high-dose radiation exposure to the heart following thoracic radiation therapy (RT) and short-term follow-up.
“Radiation therapy is standard of care for some patients with thoracic malignancies such as lung cancer, esophageal cancer, thymoma, or malignant mesothelioma. Radiation exposure to the heart is avoided when possible but even with advanced radiation therapy techniques there are instances when high radiation exposure to the heart is inevitable. The effects of acute high-dose exposure are not well defined.
“Researchers at The University of Texas MD Anderson Cancer Center prospectively evaluated the cardiac function biomarkers brain natriuretic peptide (BNP), troponin-I (TNI), and electrocardiogram (ECG) in 25 patients receiving high-dose conformal radiation therapy for thoracic malignancies. Expected exposure to the heart was ≥20 GY. Biomarker measurements were taken before RT, within 24 hours of the first dose, on the day of the last dose, and at first follow-up 1-2 months after completion of RT.”
“Western Australian researchers have determined the risk of developing mesothelioma continues to increase even 40 years after a person’s first exposure to asbestos.
“The Curtin University and UWA School of Public Health study is one of the first of its kind and investigated 22,048 people exposed to asbestos across the globe using data from six cohort studies of exposed workers and two of residential exposures.
“Pleural and peritoneal mesothelioma are cancers that develop on the lining of the lungs and are almost always caused by asbestos exposure.
“Researchers used conditional logistic regression to model the relationship between the time since first asbestos exposure and the risk of pleural mesothelioma and the rarer peritoneal mesothelioma.
“They found the rate and risk of pleural mesothelioma increased until 45 years after the first exposure. After 45 years the risk rate then appeared to slow down.
“However, the rate of peritoneal mesothelioma over 10-50 years continued to increase.”
“In light of nonrandomized studies suggesting benefit of video-assisted thoracoscopic partial pleurectomy (VAT-PP) in symptom control and survival, Rintoul et al performed a randomized trial (MesoVATS) of VAT-PP vs talc pleurodesis in malignant pleural mesothelioma. As reported in The Lancet, this UK study showed no survival improvement, more frequent complications, and longer hospital stay with VAT-PP.”
Editor’s note: A study with volunteer mesothelioma patients aimed to compare two treatments: video-assisted thoracoscopic partial pleurectomy (VAT-PP) and talc pleurodesis. All patients in the trial had malignant pleural mesothelioma with pleural effusion. The researchers wished to figure out which treatment was better in terms of symptom control and survival. They found that, between the two treatments, there was no significant difference in the number of patients still alive one year later. Also, patients treated with VAT-PP had more frequent complications and longer hospital stays.