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Second-Line Immunotherapy Treatment Fails to Improve Mesothelioma Survival

A large international clinical trial of the immunotherapy drug tremelimumab as a second- or third-line treatment option for malignant mesothelioma has produced some disappointing news.

Drug maker AstraZeneca has just released an update on the ongoing DETERMINE trial which suggests that the survival rates are roughly the same for previously-treated mesothelioma patients whether they later received treatment with tremelimumab or a placebo.

What is Tremelimumab?

Cancer cells have the unique ability to thwart the immune system. Tremelimumab is a monoclonal antibody designed to disrupt that ability. It does this by binding to the protein CTLA-4 on the surface of white blood cells, preventing the protein from inhibiting the body’s normal cancer-fighting power.

By disabling CTLA-4, tremelimumab is supposed to stimulate the immune systems of patients with malignant mesothelioma and some other cancers to attack their tumors. But the results of the DETERMINE trial suggest that the drug does not work as well as was originally hoped.

The DETERMINE Mesothelioma Trial

The DETERMINE trial is a double-blind, placebo-controlled, phase 2b trial conducted at 105 study sites in 19 countries. Although it is still ongoing, it is no longer recruiting new mesothelioma patients.

Between May 2013 when the trial started and December 2014, 571 patients with unresectable mesothelioma (pleural or peritoneal) were randomly assigned to receive either tremelimumab or a placebo drug once a month for 7 months, and then once every three months. Neither the doctors nor the patients knew which drug each patient was receiving.

According to an update recently published in The Lancet Oncology, as of January 2016, 307 of the 389 mesothelioma patients (80%) in the tremelimumab group and 154 of the 189 patients (81%) in the placebo group had died.

Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7.7 months in the tremelimumab group and 7.3 months in the placebo group,” reports lead investigator Michele Maio, MD, of the University of Siena in Italy.

Patients in the trial had all received previous chemotherapy but were no longer on other treatments when they were being given tremelimumab.

Does Tremelimumab Have a Future?

Since tremelimumab does not seem to be effective as either a stand-alone therapy for malignant mesothelioma or as a second- or third-line treatment option, investigators will shift their focus to studies of the drug in combination with other mesothelioma treatments.  

There is some reason to remain hopeful about its prospects. A small Columbia University study of tremelimumab in combination with another monoclonal antibody called durvalumab found a 23% tumor response rate in people with non-small cell lung cancer.


Maio, M, et al, “Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial”, July 17, 2017, The Lancet Oncology, Epub ahead of print

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