From the blog

SMARTEST Trial Hopes to Improve Survival Times for Mesothelioma

Published: July 1, 2022

Researchers are performing a clinical trial hoping that they can make pleural mesothelioma a more manageable, and even survivable, disease. The clinical trial is being done at Princess Margaret Cancer Center in Toronto. The trial is known as SMARTEST, which stands for Surgery for Mesothelioma After Radiation Therapy using Exquisite Systemic Therapy. Researchers in the trial are hoping to find an effective therapy for mesothelioma with very little toxic side effects. There is still no cure for the disease, so doctors hope this research will help find a better way to control pleural mesothelioma in the future.

There are multiple steps to the treatment. First, patients are given low dose radiation and then low dose cyclophosphamide, which acts as immunotherapy and an immunosuppressant. Patients are then given aggressive surgery and then a round of immunotherapy drugs including tremelimumab and durvalumab. This builds on previous trials known as the SMART protocol. The study is going to consist of 30 patients who have not had prior treatment and qualify for aggressive surgery. They also need to be either stage I, II, or III. Pleural mesothelioma is a hard-to-treat cancer caused primarily by inhalation of asbestos fibers. The standard treatment for the illness is chemotherapy, but it does not work very well. Many patients don’t live a year past diagnosis. The immunotherapy combination of Opdivo and Yervoy were approved in 2020 for mesothelioma, but only a small number of patients benefit from this treatment.

Cancer specialists believe that immunotherapy is the future of mesothelioma treatment but will not be a standalone treatment for the disease. Other immunotherapy trials are being done for mesothelioma to find a good combination therapy. One such study is looking at the approved drugs Opdivo and Yervoy alongside stereotactic body radiation therapy. Other trials include Opdivo being used with chemotherapy before surgery and another study consists of intensity modulated radiation therapy and chemotherapy after surgery. The previous SMART trial consisted of 19 patients with epithelioid mesothelioma that had no lymph node involvement. The median survival was 5.5 years, which is the first time a multimodal therapy improved survival past five years. When all cases were considered, the median survival was 24.4 months and disease-free survival was 18 months. Patients in the SMART trial did not receive immunotherapy but instead received a higher dose of radiation before the entire diseased lung was removed, a surgery known as extrapleural pneumonectomy.

The treatment utilizes radiation therapy to stimulate the immune system. This prevents cancer from spilling or seeding into the chest cavity while surgery is performed, reducing the chance of mesothelioma recurring. The SMARTER trial in Toronto utilizes a low dosage of radiation and pleurectomy and decortication surgery, which does not remove the lungs. This surgery is sometimes preferred because there is a shorter recovery time after this procedure. Immunotherapy drugs are also not used. SMARTER utilizing the lung sparing surgery allowed more patients to be studied because it could include patients who were not in good enough shape for their lungs to be removed. Data from SMARTER has not been released, but the trial is not expected to reach the same survival times as SMART. SMARTEST is also using lung sparing surgery and low dose radiation but is adding cyclophosphamide before surgery and immunotherapy after surgery, which can improve survival without the toxicity of standard chemotherapy. It is supposed to be like the SMART trial without the longer and rougher recovery period.

“—SMARTEST Trial—” (May 19, 2022). [Link]
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