From the blog

A Combination of Tremelimumab and Durvalumab Can Extend Mesothelioma Survival

Published: April 23, 2021

An Italian study has found that the combination of two immunotherapy drugs can create a long-term survival in mesothelioma patients. The two drugs, tremelimumab and durvalumab, were just given orphan drug status to treat liver cancer in the last year. The best results in the mesothelioma study were seen in patients with a high level of mutated genes. Patients typically only live one year after diagnosis but one patient in the study lived for 41 months.

White blood cells are able to fight cancer cells naturally, but mesothelioma cells are able to block it using the protein CTLA-4. Tremelimumab works by binding to the CTLA-4 protein on white blood cells, preventing the protein from inhibiting their effectiveness at fighting cancer. Unfortunately, tremelimumab has been tested for mesothelioma on its own with poor results. Durvalumab could be the key to getting tremelimumab to work effectively on mesothelioma though. It works by blocking the protein PD-L1, which disguises mesothelioma cells, allowing them to hide from the body’s natural defenses. The people who have a lot more of this protein than is considered normal respond to durvalumab the best. The study is a follow up to the NIBIT-MESO-1 trial and is showing to be an effective treatment for people unable to receive surgery.

The NIBIT-MESO-1 trial had 40 patients who either had peritoneal or pleural mesothelioma and were unable to receive surgery. The patients received a combination of tremelimumab and durvalumab every four weeks a total of four times. They were then given durvalumab by itself every four weeks for a total of nine times. If patients had their cancer come back after having a successful response during the first trial, they could receive the same treatment again to be studied, which happened with 17 patients. They were administered at least one dose of the immunotherapy combination the second time. Seven of the patients had immune related stable disease during the trial. During the follow up period, the patients who were retreated had a median overall survival of 12.5 months.

During the study, researchers found that the best results were in the patients with the highest level of mutated cells in their mesothelioma tumors. This is the case because the drugs target different proteins that are overexpressed when certain genes are mutated. Patients who had a higher mutational burden than the median of 8.3 had their lives extended 2.5 times longer than patients with fewer gene mutations (41.3 months vs. 17.4 months).

“A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1)” Clinical Trials [Link]
Luana Calabrò, MD et al., “Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study” (April 9, 2021). [Link]
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