Immune checkpoint inhibitors are a class of immunotherapy drugs that help the immune system fight cancer. Clinical trials are currently testing these drugs on mesothelioma.
Immune checkpoint inhibitors target specific proteins on the surface of cancer cells called antigens. In turn, the inhibitory effects of tumor cells on immune cells are minimized. This allows the immune system to better control the cancer
Clinical trials are testing these innovative drugs to discover if they could play a role in the treatment of mesothelioma.
None of these immunotherapy drugs have been approved to treat mesothelioma by the U.S. Food and Drug Administration (FDA), but several ongoing clinical trials could lead to approval.
Yervoy was approved in 2011 to treat melanoma.
Keytruda was approved in 2014 to treat melanoma and was later approved to treat lung cancer, head and neck cancer, Hodgkin lymphoma, bladder cancer, gastric cancer and solid tumors with certain biomarkers.
Opdivo was approved in 2014 to treat melanoma and was later approved to treat lung cancer, kidney cancer, Hodgkin lymphoma, head and neck cancer, bladder cancer, colorectal cancer and liver cancer.
Atezolizumab (Tecentriq) was approved in 2016 to treat bladder cancer and was later approved to treat lung cancer.
Avelumab (Bavencio) was approved in 2017 to treat Merkel cell carcinoma and bladder cancer.
Imfinzi was approved in 2017 to treat bladder cancer.
Research on mesothelioma has shown that several immune checkpoint inhibitors are effective against the asbestos-related cancer, especially Keytruda and the combination of Opdivo and Yervoy.
Checkpoint inhibitors are antibodies that block antigens on the surface of cancer cells or block proteins on immune cells called T cells. Antigens work like a mask to hide cancer cells from the immune system.
These antigens are also called immune checkpoints.
Drugs that inhibit checkpoint antigens effectively unmask cancer cells, allowing the immune system to recognize and attack the cancer.
The antigens that checkpoint inhibitors block include CTLA-4 and PD-L1.
Imfinzi targets PD-L1.
Yervoy and tremelimumab target CTLA-4.
Keytruda and Opdivo target PD-1, a checkpoint protein on the surface of T cells. PD-1 normally attaches to PD-L1. By preventing this interaction, T cells are not fooled into thinking cancerous cells are healthy, allowing for an immune response.
Out of all of these drugs, Keytruda is the most well-known. In 2015, former U.S. President Jimmy Carter said Keytruda put his malignant melanoma into remission.
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Immune checkpoint inhibitors can cause side effects that are similar to other anti-cancer treatments such as chemotherapy and radiation therapy.
A concern with immune checkpoint inhibitors is that they may cause the immune system to attack healthy cells and organs. Because they serve to stimulate the immune system against cancer, it can lead to serious side effects.
These serious side effects are less common and usually affect the following organs: lungs, liver, intestines, kidneys and the endocrine glands.
The majority of mesothelioma clinical trials testing these drugs involve two immune checkpoint inhibitors. Combining drugs that target different antigens has a synergistic effect.
Some trials combine immune checkpoint inhibitors with chemotherapy or a mesothelioma vaccine.
Positive results from phase I and phase II trials of Yervoy and Opdivo in mesothelioma patients has led to a phase III clinical trial.
This is significant because phase III trials for mesothelioma are rare. It isn’t common for a therapy to work well enough in a phase II mesothelioma trial to warrant further study. Researchers have high hopes for this study.
Trials of Imfinzi and tremelimumab in mesothelioma patients began in 2016 and 2017. These trials are too new to produce results.
However, in 2015, an Italian clinical trial that combined these drugs proved clinical activity in mesothelioma, which means the study proved these drugs are effective but did not prove whether the drugs improved survival.
In 2017, the Seattle Cancer Care Alliance opened a phase II clinical trial combining Imfinzi with the chemotherapy drugs cisplatin and pemetrexed (Alitma).
In 2017, the Moffitt Cancer Center in Tampa, Florida, opened a phase II clinical trial combining Keytruda with the mesothelioma vaccine CRS-207. The trial is available at five other cancer centers in the U.S.
Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators. Read More