“Combination immunotherapy as second or third line treatment extends overall survival to at least 15 months in patients with pleural malignant mesothelioma, according to late-breaking results from the MAPS2 trial presented today at the ESMO 2017 Congress in Madrid.
“Malignant pleural mesothelioma (MPM) is a rare disease usually caused by occupational exposure to asbestos. First line therapy is pemetrexed and platinum chemotherapy, with or without bevacizumab. There is no approved second line treatment and drugs that have been tested in this setting had low efficacy, with a disease control rate under 30%. Phase II studies have shown promising activity of checkpoint inhibitors as second line treatment.”
“Pembrolizumab, an antibody drug already used to treat other forms of cancer, can be effective in the treatment of the most common form of mesothelioma, according to a new study led by investigators from the Perelman School of Medicine at the University of Pennsylvania. The study, published this month in The Lancet Oncology, is the first to show a positive impact from checkpoint inhibitor immunotherapy drugs on this disease.
“Malignant pleural mesothelioma is a rare and aggressive cancer that represents about 90 percent of all malignant mesothelioma cases. It’s primarily caused by the inhalation of asbestos, a fiber commonly found in some forms of insulation, vinyl floor tiles, and other material. Tumors form in the pleura, a thin membrane of cells that line the lungs and chest wall. Most patients survive less than a year. This poor prognosis is partially due to the fact that most patients are not diagnosed until they are already at a late stage of the disease. The standard first-line therapy treatment involves chemotherapy, and currently there is no approved second-line therapy.”
“A new statistical model may help predict which patients are most likely to receive life-extending benefits from surgical treatment for malignant pleural mesothelioma (MPM), according to an article in the September 2015 issue of The Annals of Thoracic Surgery.
“MPM is an aggressive cancer that affects the lining of the chest cavity (pleura). The main cause of mesothelioma is believed to be repeated exposure to asbestos, which is a naturally occurring group of minerals found in soil and rocks around the world. Asbestos was previously used to make fireproof materials, such as theater curtains, insulation, flooring, and workers’ gloves, and is still used in some products today. About 3,000 cases of mesothelioma are diagnosed in the US each year, with many more worldwide. There is frequently a lag time of twenty years or more between exposure to asbestos and the development of the disease.
“Currently, there is no cure for advanced stage mesothelioma, and the 5-year survival rate is only about 10%.”
A study in 25 patients with mesothelioma, a type of lung cancer associated with exposure to asbestos, suggests that radiation treatment before surgery can significantly increase survival. Patients were treated using a new approach dubbed SMART (Surgery for Mesothelioma After Radiation Therapy). They received an accelerated, 5-day course of intensity-modulated radiation therapy (IMRT), which conforms the radiation dose around the tumors while sparing nearby healthy tissues. They then underwent surgery to remove the affected lung. Seventy-two percent of patients survived 3 years or more after treatment; 3-year survival rates without SMART rank at 32%. People with known exposure to asbestos who experience shortness of breath, weight loss, and fatigue for more than 3 weeks should be evaluated by a doctor to ensure speedy access to treatment.
Mesothelioma is a form of lung cancer strongly associated with exposure to asbestos. Even though asbestos has been banned or heavily regulated in most developed nations, due to delayed onset, the number of mesothelioma cases is predicted to climb until around 2020. In the UK, which has the highest mesothelioma incidence worldwide, two new clinical trials are aiming to find treatments for the disease. The Meso2 trial will investigate ganetespib, while the COMMAND trial will examine defactinib. Defactinib specifically targets cancer stem cells, which often survive cancer treatment and cause cancer recurrence. The drug may therefore help prevent relapse after first-line therapy.
Schuberth PC, Hagedorn C, Jensen SM, Gulati P, et al. Journal of Translational Medicine. Aug 12, 2013.
Malignant pleural mesothelioma (MPM) results from chronic exposition to asbestos in at least 70% of the cases. Fibroblast activation protein (FAP) is predominantly expressed on the surface of reactive tumor-associated fibroblasts as well as on particular cancer types. Because of its expression on the cell surface, FAP is an attractive target for adoptive T cell therapy. T cells can be re-directed by retroviral transfer of chimeric antigen receptors (CAR) against tumor-associated antigens (TAA) and therefore represent a therapeutic strategy of adoptive immunotherapy.
FAP re-directed CD8+ T cells showed antigen-specific functionality in vitro and in vivo. Furthermore, FAP expression was verified in all MPM histotypes. Therefore, our data support performing a phase I clinical trial in which MPM patients are treated with adoptively transferred FAP-specific re-directed T cells.
Annals of Cancer Research and Therapy | Sep 28, 2012
Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.
Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf
Cancer Chemotherapy and Pharmacology | Jan 12, 2013
The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.
A retrospective study in Japan examined 55 patients aged 75 years or over with inoperable non-small cell lung cancer (NSCLC) who had a mutation in the EGFR gene and received gefitinib (Iressa) as first-line therapy. The treatment was generally well tolerated and patients experienced longer periods without cancer progression (median: 13.8 months) and longer overall survival (median: 29.1 months) than commonly reported for similar patients. While studies using control groups will need to confirm that Iressa is indeed more effective than standard chemotherapy or a placebo, these findings suggest that Iressa may be a preferable first-line treatment in elderly patients with advanced EGFR-mutant NSCLC.