Immunotherapy Drug May Be Option for Advanced Mesothelioma

Advanced malignant mesothelioma patients who have not responded to standard chemotherapy may have an alternative in a new drug called tremelimumab. An open-label, single-arm, phase 2 trial of the drug has found it to be safe and tolerable and to have “encouraging clinical activity” in advanced malignant mesothelioma that cannot be surgically removed.

Tremelimumab is a monoclonal antibody that acts on a particular downregulator of the immune system called cytotoxic T-lymphocyte antigen 4 (CTLA4). The goal of tremelimumab is to inhibit the immune system tolerance to tumors, which tends to allow them to grow unchecked. When CTLA4 is reactivated with a drug like tremelimumab, it regains its ability to attack tumors.

The new published study on tremelimumab for mesothelioma was conducted in Italy. Patients were eligible for the trial if they had unresectable mesothelioma that had continued to grow after first-line platinum-based chemotherapy. As long as patients had a life expectancy of at least 3 months, they received 15 mg of intravenous tremelimumab every 3 months until either the disease responded or the treatment itself proved too toxic.

Twenty-nine patients with advanced mesothelioma were enrolled in the study between May 2009 and January 2012. All patients received at least one dose of tremelimumab. Although no patients had a complete response, meaning their mesothelioma tumors were eradicated, two patients (7%) did have a partial response, one lasting 6 months and the other lasting 18 months. In 31% of patients, the researchers noted “disease control” meaning their mesothelioma stopped growing at its previous rate. The median time until mesothelioma began to progress again was 6.2 months and the median overall survival was 10.7 months.

Most patients in the study did experience at least one grade 1-2 “adverse event” or complication from the treatment and four patients had more serious complications. Given that there are few conventional treatment options for mesothelioma and even fewer options for advanced mesothelioma patients who have failed first-line therapy, the research team concluded that tremelimumab showed promise and had an acceptable safety and tolerability profile.

Source:

Calabro, L, et al, “Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial”, September 10, 2013, The Lancet Oncology, Epub ahead of print.