Why Immunotherapy Before Surgery Works for Treating Mesothelioma

Give another win to immunotherapy for mesothelioma.

Ever since 2020, when the U.S. Food and Drug Administration approved an immunotherapy combination for malignant pleural mesothelioma, more data has emerged in support of mesothelioma immunotherapy treatment.

Two new studies have found the latest: immunotherapy before surgery elevates survival for patients.

As of the beginning of 2023, the immunotherapy combination of Opdivo and Yervoy are approved for malignant pleural mesothelioma when surgery is not an option. However, some clinical trials at the top cancer centers are testing immunotherapy with surgery – either before or after, or both.

The results of these studies continue to affirm that immunotherapy for mesothelioma is better from a life expectancy and survival standpoint than chemotherapy for mesothelioma. This data continues to pave a path for immunotherapy treatment to be a staple of multimodal mesothelioma therapy.

 

What Is Immunotherapy for Mesothelioma?

Immunotherapy for mesothelioma is a medical treatment for cancer. The treatment helps strengthen the immune system and create a stronger immune response against cancer.

There are immune cells – most notably, T cells – in charge of defending the body from diseases such as cancer. However, these cells struggle to fight cancer due to a treacherous environment around tumors and the speed at which cancer grows. The immune system needs outside help – from medical science – to match the strength of cancer.

Immunotherapy can work in a variety of ways to treat mesothelioma:

• Neutralizing an immune system-suppressing gene or protein on mesothelioma tumor cells
• Amplifying a cancer-fighting gene or protein on immune system cells
• Guiding immune system cells to cancer cells quicker to speed up the immune response

Immune Checkpoint Inhibitors for Mesothelioma

The type of immunotherapy that’s most advanced for mesothelioma is called immune checkpoint inhibitor. Opdivo and Yervoy are immune checkpoint inhibitors. The pair improved survival for pleural mesothelioma patients by an average of 4 months compared to chemotherapy:

• Median survival from Opdivo and Yervoy was 18.1 months.
• Median survival from chemotherapy was around 14 months.

Keytruda, which is approved by the FDA for a very small subset of mesothelioma cases, is also an immune checkpoint inhibitor.

Immune checkpoint inhibitors neutralize an immune-suppressing protein on cancer cells. Mesothelioma cells, in particular, have surface proteins that link up with surface proteins on the immune system’s T cells. When the proteins bind together, the surface proteins essentially tell the T cells to “stand down.” The T cells ignore the mesothelioma cells as a threat to the body.

Immune checkpoint inhibitors block these surface proteins from linking. Opdivo and Keytruda block PD-1 (on T cells) and PD-L1 (on mesothelioma cells) from connecting. Yervoy blocks CTLA-4 (on T cells) and B7 (on mesothelioma cells).

Many scientists use the automobile brakes analogy when explaining immune checkpoint inhibitors. They say the cancer therapies “take the brakes off” of T cells, allowing the immune system to go full speed at attacking mesothelioma tumors.

 

Explaining Multimodal Therapy for Mesothelioma

To best understand why immunotherapy works well with surgery, let’s first explain the theory behind multimodal therapy for mesothelioma. Doctors vouch for using multiple types of cancer therapy to treat aggressive cancers like mesothelioma.

“Surgery itself may not be curative, however combining surgery with some other modality of therapy often provides benefit,” said Dr. Bryan Burt, chief of the Division of Thoracic Surgery at Baylor College of Medicine.

The main types of cancer therapy have long been:

• Surgery
• Chemotherapy
• Radiation

Immunotherapy is emerging as a fourth main type of cancer treatment.

Mesothelioma doctors believe fighting this cancer in multiple ways – in different stages of treatment – is most effective for giving patients the longest survival possible, potentially even curing them.

Surgery is the quickest way to take out mesothelioma cells. Chemotherapy kills healthy and diseased tissue in an attempt to wipe out remaining cancer cells. Radiation is a more targeted therapy aiming to burn cancer tissue and kill the cells.

 

Immunotherapy Improves Immune System Activity Before Surgery

Baylor College of Medicine researchers looked into what they called “preoperative immunotherapy for mesothelioma.” The term “preoperative” means before surgery.

They gave patients two immune checkpoint inhibitors: durvalumab and tremelimumab. These two are similar to Opdivo and Yervoy:

• Durvalumab, like Opdivo, blocks the proteins PD-1 and PD-L1.
• Tremelimumab, like Yervoy, blocks CTLA-4 and B7.

They found that the combination of durvalumab and tremelimumab changed the environment around mesothelioma tumors in the immune system’s favor. There were more T cells capable of fighting mesothelioma in the area.

They believe the higher activity of T cells improves the chances of mesothelioma surgery eliminating most, if not all, of the tumor cells.

 

Immunotherapy Before Surgery Leads to Better Mesothelioma Survival

The other main study backing up immunotherapy in multimodal treatment was published in Physician’s Weekly. The trial included 179 patients and split them into four groups:

• Chemotherapy only
• Immunotherapy with or without chemotherapy
• Surgery with chemotherapy
• Surgery with immunotherapy and chemotherapy

The last group – receiving surgery, immunotherapy and chemotherapy – did the best. They had an average survival of 22.6 months. The group receiving surgery and chemotherapy – without immunotherapy – was around 20 months.

Immunotherapy and chemotherapy – without surgery – was at 18 months. Chemotherapy alone was at 11 months.

Researchers said the longest survival times were in patients who had “surgery and immunotherapy as part of multimodal treatment protocols.”

Mesothelioma Guide can help you find a cancer hospital offering immunotherapy for mesothelioma. We can also help you search for clinical trials with immunotherapy and surgery together.

Email our registered nurse and patient advocate, Karen Ritter, at karen@mesotheliomaguide.com for help finding a hospital or top cancer center offering immunotherapy.