Mesothelioma is an aggressive cancer with no cure. However, in recent years, researchers have developed and continue to improve new diagnostic methods and treatments that can potentially lead to a cure.
Because mesothelioma has a long latency period and nonspecific symptoms, it has often been noted as difficult to treat and having a poor prognosis. Despite these challenges, various clinical trials for emerging treatments and diagnostic tests have shown promise in being able to detect mesothelioma earlier and improve prognosis. While there is currently no cure for malignant mesothelioma, researchers and doctors have been able to extend patient life expectancies longer than ever before with multimodal treatment plans using experimental treatment options.
Advancements in Treatment Modalities
As mesothelioma awareness increases, more research dollars and time are being spent on testing and improving standard therapies, and studying impacts of combining these therapies with newer modalities, such as immunotherapy.
Updates to Traditional Treatments
For peritoneal mesothelioma patients, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve survival for patients whose disease is diagnosed in the early stages. In one study, more than 50 patients treated with a CRS and HIPEC combination achieved median overall survival of 97.8 months. However, further studies are needed to test the efficacy of the treatment for peritoneal mesothelioma patients diagnosed in the later stages of disease, which currently occur more often than early diagnoses.
The most encouraging development in chemotherapy treatment in recent years has been the success found with bevacizumab, sold as Avastin. When the drug was added to treatment with standard chemotherapy drugs (pemetrexed and cisplatin), pleural mesothelioma patients experienced improved survival rates. One study found patients treated with bevacizumab in addition to pemetrexed plus cisplatin achieved median survival of 18.8 months. Comparatively, patients in the same study treated with just pemetrexed and cisplatin had a median overall survival of 16.1 months.
One of the most promising additions to mesothelioma radiation treatment is intensity-modulated radiotherapy (IMRT). The therapy is among the most common types of radiation therapy now used for most mesothelioma patients. One study found using IMRT prior to surgical treatment with extrapleural pneumonectomy extended median patient survival to 36 months. The average malignant pleural mesothelioma life expectancy is six months to one year.
Emerging Cancer Treatments
In addition to analyzing necessary adjustments and improvements to the standard treatments, researchers are testing emerging cancer treatments as potential adjuvant, neoadjuvant and first- and second-line therapies. Promising new treatments include gene therapy and immunotherapy, specifically cancer vaccines and Keytruda.
Gene therapy treats mesothelioma cancer by introducing new genes to the patient's body. These genes, often given through virus vectors, invade the mesothelioma tumors, making it easier for the body’s own immune system to attack and kill the cancer cells. A 2016 study found pleural mesothelioma patients previously treated with chemotherapy who underwent gene therapy followed by a second round of chemotherapy achieved a median overall survival of 21.5 months, with a 2-year survival rate of 32%. The patients were treated using the human interferon-alpha2b gene (Ad.IFN).
A second group in the study received gene therapy and then their first round of chemotherapy. This group had a median overall survival of 12.5 months. These findings suggest that gene therapy given between two rounds of chemotherapy creates the most favorable outcomes for pleural mesothelioma patients. However, both groups in the study achieved median overall survival times longer than the average survival time for pleural mesothelioma patients, which is about one year. Further study is required to determine the best therapies to combine with gene therapy, though the results of this study along with the tolerability of the treatment gives hope.
Immunotherapy uses a patient’s own immune system to fight their cancer. Immunotherapy drugs help differentiate cancer cells from normal healthy cells, enabling the body to better detect and target cancerous tumors. The ability to attack the cancerous tumors and not blindly kill all cells creates less harmful side effects for the mesothelioma patients. Two of the most promising immunotherapy treatments for mesothelioma patients are cancer vaccines and Keytruda.
A cancer vaccine uses cancer cells and the body’s immune system to treat a patient's mesothelioma cancer. The vaccines use immune system memory to treat the cancer, with the hope that the treatment will persist long after the vaccination. There is currently no cancer vaccine approved by the U.S. Food and Drug Administration (FDA) for the treatment of mesothelioma, but there has been success using the therapy for the cancer in clinical trials.
One trial using a dendritic cell cancer vaccine found promising results. Seven out of the 10 pleural mesothelioma patients treated with the vaccine achieved survival of at least 24 months. Greater still, two patients were alive 50 and 66 months after treatment. While the clinical trial was small, the favorable patient outcomes confirm the need for further studies into mesothelioma cancer vaccines.
Keytruda, generic name pembrolizumab, is an immune checkpoint inhibitor that blocks the PD-1/PD-L1 gene pathway. Blocking the pathway enables the immune system to identify and kill cancer cells. The drug is currently approved by the FDA for use in non-small cell lung cancer (NSCLC), hodgkin's lymphoma and melanoma. While not specifically approved for the treatment of mesothelioma cancer, the drug has been successful in clinical trials.
One trial, KEYNOTE-028, found that of the 25 pleural mesothelioma patients they treated with the drug, 52% had stable disease following treatment. Additionally, the trial reported a patient median overall survival of 18 months. More than 62% of patients in the trial achieved 12-month survival, which is currently the average survival time for pleural mesothelioma patients. The trial shows that Keytruda is a promising mesothelioma treatment option, and also proved that the drug is safe for long-term use by patients as there were minimal side effects reported.
Areas that Require More Research
Advancements in mesothelioma cancer research are being made every single day. Cancer treatments are being improved, scientists are creating more effective new drugs and mesothelioma survivors are living longer than ever. However, in order to find a cure, there are obstacles that need to be addressed. Symptom latency and the variety of genomic alterations within the cancer are two of the roadblocks that healthcare professionals need to overcome in their search for a mesothelioma cure. Thankfully, progress is being made.
Early Detection to Combat the Latency of Symptoms
A major hurdle in the fight for a mesothelioma cure is late diagnosis of patients. When diagnosed in the later stages of disease (stage 3 or 4), patients may be ineligible for aggressive treatment modalities, such as certain surgical treatments, due to the metastasis of tumors.
Unfortunately, early detection is rare. Patients are often not diagnosed until the later stages because the cancer does not manifest until decades after initial asbestos exposure. Once symptomatic, patients may not receive an accurate diagnosis due to the common, nonspecific nature of mesothelioma symptoms. For instance, pleural mesothelioma may be misdiagnosed as the common cold or influenza.
However, researchers have begun to make progress toward being able to diagnose mesothelioma in the earlier stages. Biomarkers and blood tests are being used to combat the difficulty associated with the latent symptoms. Researchers in a 2016 study were able to accurately identify malignant mesothelioma in 17 patients between 4 – 10 years prior to symptom manifestation. The researchers tested serum samples from the asbestos exposed individuals for presence of ENOX2, which is a known cancer marker. Their findings require further research to identify if this particular biomarker may be viable on a larger scale.
Biomarkers that are already widely used for mesothelioma include MESOMARK, HMGB1 and N-ERC/Mesothelin test. While these tests are not enough to diagnose mesothelioma patients, they can be used to identify if further more invasive procedures, like a biopsy, are needed for diagnosis.
Once diagnosed, proper initial staging of the cancer is the first step to best treating a patient's specific mesothelioma case, and leads to the most favorable outcomes. Researchers have found that a PET-CT works best to determine cancer stage and predict patient outcomes. Once staged appropriately, the most aggressive viable treatment option can be administered. Accessing treatment early is proven to increase survival rates. A group of pleural mesothelioma patients in France achieved a 46% 5-year survival rate when diagnosed at the early stages of disease and treated with a multimodality approach. On average, studies have found the 5-year survival rate for pleural mesothelioma is 12%.
Variety of Genomic Alterations
Once diagnosed, the variety of genomic alterations within mesothelioma on a per patient basis further complicates the treatment of the cancer. Patients may have between 1 – 5 genomic alterations, which makes it critical to know the treatment that is most effective for each genomic defect. Studies have found that each patient’s molecular portfolio is different, suggesting that personalized medicine may be necessary for treatment of mesothelioma patients, specifically patients presenting with pleural mesothelioma. The most common alterations for mesothelioma patients occur in the BAP1, NF2, CDKN2A/B and P53 genes. Ongoing clinical trials are focusing on treating these specific genomic alterations to find a cure for mesothelioma cancer.
While there is still no cure for mesothelioma, the improvements made within mesothelioma treatments and diagnostic tests give hope for the future. Patients are able to fight their cancer with new tools that have enabled some patients to survive for years beyond their initial prognosis. Those diagnosed with mesothelioma should discuss all potential treatment options with their medical team to decide which options may provide the most favorable outcome.
Author: Linda Molinari
Editor in Chief, Mesothelioma Cancer AllianceRead about Linda
Reviewer: Annette Charlevois
Patient Support CoordinatorRead about Annette
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