A historic clinical trial is now beginning to test a new protocol for how to treat the deadly cancer called mesothelioma.

SMARTEST for mesothelioma is a potentially groundbreaking approach to caring for mesothelioma patients. The protocol is an evolution of two earlier approaches: SMART for mesothelioma and SMARTER for mesothelioma.

The clinical trial is at University Health Network in Toronto, Ontario, Canada. University Health Network includes the Princess Margaret Cancer Center. The trial opened May 19, 2022 and is now accepting patients.

 

What Is SMARTEST for Mesothelioma?

SMARTEST for mesothelioma uses radiation before surgery for mesothelioma, and then follows surgery with immunotherapy. The approach tries to shrink mesothelioma tumors to make surgery easier. Then the immunotherapy drugs control the lingering cells left after surgery and kill them off.

The SMARTEST trial is a phase 2 study with up to 30 participants. Anyone who wants to join must be a candidate for aggressive mesothelioma surgery: either pleurectomy/decortication or extrapleural pneumonectomy.

Following surgery, patients receive the immunotherapy drugs tremelimumab and durvalumab. Tremelimumab and durvalumab are immune checkpoint inhibitors. These immunotherapies block certain cancerous proteins that subdue the immune system.

Tremelimumab is a blockade for CTLA-4 and B7, two proteins that connect and help mesothelioma tumors hide from the immune system’s T cells. Durvalumab keeps PD-1 and PD-L1 apart. These two proteins also block the T cells’ activity.

Immunotherapy is growing in popularity as a treatment for mesothelioma and many other types of cancer. The U.S. Food and Drug Administration authorized mesothelioma patients to use two immunotherapy drugs: Opdivo (nivolumab) and Yervoy (ipilimumab). These two drugs are also immune checkpoint inhibitors.

The median survival for Opdivo and Yervoy is around 18 months. However, long-term survival of multiple years is still rare when patients only receive immunotherapy treatment.

Many specialists believe the way to achieve long-term survival from mesothelioma is with multiple types of treatment. This approach is called multimodal therapy for mesothelioma. The question left to answer is which therapies to combine together and what order to use them.

SMARTEST is a multimodal therapy approach to mesothelioma. The order of radiation first, surgery second, and immunotherapy third is innovative and the first of its kind.

Experts believe radiation therapy can ignite the immune system to fight cancer. Radiation burns tissue around the lung cavity and inspires T cells and natural killer cells to swarm to the site where the burning and inflammation of tissue occurs.

This belief is why Princess Margaret Cancer Center doctors are using immunotherapy with radiation therapy. The trial will reveal whether the activated immune system is even stronger thanks to durvalumab and tremelimumab.

SMARTEST for mesothelioma is a progression from SMART for mesothelioma and SMARTER for mesothelioma.

 

SMART and SMARTER for Mesothelioma

SMART for mesothelioma stands for “Surgery for Mesothelioma After Radiation Therapy.” SMART began at a clinical trial at Princess Margaret Hospital. Dr. Marc de Perot led the protocol. SMART is now a mainstay at many U.S. cancer centers, including Michigan Medicine, led by Dr. Elliot Wakeam.

The surgery for SMART is extrapleural pneumonectomy. This surgery removes the lung affected by mesothelioma tumors.

People diagnosed with pleural mesothelioma can live with just one lung after surgery. The quality of life is lower but many patients can live happily.

SMARTER uses pleurectomy/decortication surgery instead of extrapleural pneumonectomy. Pleurectomy/decortication does not remove the lung but rather takes out the pleura (lining of the lung cavity), diaphragm, and visible tumors in the lung cavity without taking out any lung tissue.

The survival rates for SMART are impressive. Nearly three-fourths of patients lived for at least three years after having radiation and surgery. The median survival for people with the epithelioid cell type was 51 months (4 years, 3 months).

When all patients were included in the results, the median survival was 24 months (2 years). This life expectancy is still nearly double that of patients who get just chemotherapy and no surgery or radiation.

 

How to Enroll in The SMARTEST Clinical Trial

We at Mesothelioma Guide encourage patients with mesothelioma to explore clinical trials. If you are unable to have surgery, joining a trial might be your best option to receive new therapies that can extend your life.

Even if you can have surgery, some clinical trials will help. The SMARTEST trial is for people eligible for surgery, so you should ask your doctor about this option.

We at Mesothelioma Guide can also help you enroll in a specific clinical trial. This study is taking place at Princess Margaret Cancer Centre in Toronto, Ontario, Canada. If you do not want to travel to Toronto, then you might have to wait until the study expands to U.S. cancer centers.

Otherwise, we can help you look for another clinical trial. There are some combining surgery and immunotherapy together. Email our lead patient advocate and registered nurse Karen Ritter at karen@mesotheliomaguide.com for more assistance.

    Sources & Author

Devin Goldan image

About the Writer, Devin Golden

Devin Golden is the content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.

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    Sources & Author

Picture of Devin Golden

About the Writer, Devin Golden

Devin Golden is the content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.