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A Treatment Involving Checkpoint Inhibitors Before Surgery is Showing Promising Results for Mesothelioma

Published: January 6, 2023

Immunotherapy before aggressive surgery shows great promise for pleural mesothelioma. The combination has shown that it can improve survival for a group of patients with pleural mesothelioma in a phase II study at Baylor College of Medicine. The treatment uses two immune checkpoint inhibitors, durvalumab and tremelimumab. The two drugs have shown that they can change the intratumoral immune system and can make surgery more effective for patients. The clinical trial was randomized and compared durvalumab alone to durvalumab and tremelimumab and no immunotherapy treatment before surgery. Durvalumab has been shown to be an effective therapy for other cancers, so researchers want to see if they can improve survival when combining it with another checkpoint inhibitor for mesothelioma.

The clinical trial started in May 2016 under the supervision of Dr. David Sugarbaker, who is known for his pioneering mesothelioma research. He later died in 2018 during patient enrollment. At the time, he was the new director of the Lung Institute at Baylor College of Medicine. There were 24 patients enrolled that were either eligible for pleurectomy and decortication or extrapleural pneumonectomy surgery. Both epithelioid and sarcomatoid subtypes of mesothelioma were enrolled. Nine patients were given durvalumab only, 11 were given durvalumab and tremelimumab, and four were given no immunotherapy treatment before surgery. Evaluation of the patients was performed at 34.1 months. The durvalumab group had a progression-free survival of 8.4 months and median overall survival of 14 months. The no checkpoint group had similar results. Patients in the immunotherapy combination group had much better results, but there are no survival results to report because three of the 11 patients are still alive.

The drug combination has a synergistic relationship, which means the drugs complement each other and help each other work more effectively. They both are made from human antibodies and allow the patient’s immune system to recognize and attack cancer cells. Durvalumab creates an antibody that negates the PD-L1 protein, which typically blocks the immune system from recognizing cancer cells. It is currently approved for the treatment of bladder cancer and some lung cancers. When tremelimumab was tested in mesothelioma it was not effective, but it can be effective when combined with other treatments. It works by blocking the CTLA-4 protein. Both drugs were given via intravenous infusion two weeks before surgery. After surgery, patients were given intraoperative chemotherapy.

Immunotherapy can be effective for mesothelioma, but its effects can be inconsistent. The first new treatment approved for mesothelioma occurred in 2020, which consists of Opdivo and Yervoy. The best and most effective treatment for mesothelioma is the combination of surgery, chemotherapy, and radiation. Many patients are not eligible for this treatment regimen though because they cannot receive the surgery. Survival for this treatment regimen is usually only around two years. New advancements in immunotherapy like the combination of durvalumab and tremelimumab are improving mesothelioma treatment. These advancements could possibly be approved because they are effective and safe for patients. This would improve the treatment landscape for mesothelioma and could possibly extend the survival of people suffering from the disease.

Hyun-Sung Lee et al., “A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma” Clinical Trials: Immunotherapy (December 20, 2022). [Link]
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