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Tremelimumab and Durvalumab are a Good Second Line Treatment for Mesothelioma

Published: September 3, 2021

Two immunotherapy drugs, tremelimumab and durvalumab, are showing to be a successful second line treatment for pleural mesothelioma when combined. This could mean that more treatments will be approved for the treatment of mesothelioma. The results of this phase II clinical trial were published in the Lancet Respiratory Medicine from the Department of Oncology at the University Hospital in Siena, Italy.

There were 40 patients who received tremelimumab and durvalumab intravenously every four weeks for a total of four doses. They then received maintenance durvalumab for nine weeks. The drugs are checkpoint inhibitors, which block certain proteins and allow the immune system to see and kill cancer cells. Durvalumab negates the PD-L1 protein, which is used by tumor cells to avoid the immune system. Tremelimumab blocks the receptor on immune cells that stops the immune system from attacking.  At the median 52-month mark, there were still five patients who were alive. During the study, more than a third had a long-lasting objective response. There were 65 percent of patients with immune related disease control while there was a median overall survival of 16.5 months, 20 percent survival at 36 months, and 15 percent survival at 48 months.

This study also looked at the safety and efficacy of retreatment of cancer utilizing checkpoint inhibitors. When people are treated with immunotherapy drugs, they are stopped after the disease progresses. There were 17 patients who were retreated. Once the patients had their disease progress after a partial response or stable disease, they were able to be retreated. The survival outcomes include 52.9 percent at 12 months and 23.5 percent at 24 months. There were no immune related effects because of retreatment. Doctors have concluded that retreatment with the same immunotherapy drugs could be an option for pleural mesothelioma. People who were retreated had a median overall survival of 25.6 months versus 11 months for those who received a second line treatment of chemotherapy. First line combination was shown to be effective in the study and could potentially become the standard treatment for mesothelioma.

The combination of drugs is also being studied at the Baylor College of medicine alongside surgery. They want to see if durvalumab alone or a combination of durvalumab and tremelimumab is more effective with surgery. Durvalumab is also in a phase III international study looking at effectiveness when combined with pemetrexed and cisplatin. Immunotherapy can be very effective for some patients, but for others it is not effective, so more studies need to be done. Nivolumab and ipilumab were approved for mesothelioma by the FDA, which was the first time a treatment was approved for mesothelioma in 20 years.

Luana Calabró 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” The Lancet Respiratory Medicine (April 9, 2021). [Link]
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