A study shows that immunotherapy and surgery for mesothelioma work.


In a recent phase II clinical trial at Baylor College of Medicine, an immunotherapy combination given to pleural mesothelioma patients prior to aggressive surgery demonstrated remarkable efficacy in extending survival.


Durvalumab and tremelimumab, two immune checkpoint inhibitors, demonstrated their capacity to effectively alter the intratumoral immune system and enhance surgical efficacy.


Durvalumab alone, which has been shown to be effective in other cancers, was compared to the two-drug combination and the absence of immunotherapy prior to mesothelioma surgery in this randomized clinical trial.


On December 5, the results of the randomized trial appeared in Clinical Cancer Research.


The study's authors came to the following conclusion: "These data indicate that neoadjuvant durvalumab plus tremelimumab orchestrates de novo systemic immune responses that extend to the tumor microenvironment and correlate with favorable clinical outcomes."


Clinical Trial Started by Dr. David Sugarbaker The clinical trial began in May 2016 as a result of Dr. David Sugarbaker's earlier appointment as the new director of the Lung Institute at Baylor College of Medicine. Sugarbaker is a legendary thoracic surgeon who pioneered the treatment of mesothelioma. Sugarbaker passed away in 2018 while enrolling patients continued.


The trial included 24 patients who had been evaluated and determined to be eligible for either extrapleural pneumonectomy or pleurectomy and decortication surgery. It included both epithelioid and sarcomatoid mesothelioma, which is harder to treat.


Neun patients received durvalumab alone, eleven received the immunotherapy combination, and four received no immune checkpoint inhibitors. At 34.1 months, the randomized patients were evaluated.


For those who received only durvalumab, the median overall survival was 14 months and the progression-free survival was 8.4 months, respectively. Similar outcomes were seen in those who did not receive checkpoint inhibitors.


Mesothelioma immunotherapy combination patients had significantly longer median overall survival and progression-free survival than the monotherapy group. Because three of the 11 patients were still alive at the time of the study's publication, no survival data were compiled.


The authors wrote, "We show that a single cycle of durvalumab and tremelimumab delivered in the neoadjuvant setting profoundly reorganizes the immune contexture of MPM tumors in patients with resectable MPM [malignant pleural mesothelioma]."


They stated that the regimen's effect on systemic immunity supports the data showing shorter survival times and lower recurrence rates.


The immunotherapy combination's effectiveness is determined by the way the drugs work in conjunction with one another. Both are made with antibodies made by humans. These antibodies basically reveal the cancer cells to the patient's immune system, allowing it to attack in different ways.


The antibody produced by durvalumab targets the PD-L1 protein, which frequently prevents the immune system from eliminating cancer cells. The U.S. Food and Drug Administration has given the medication, which goes by the brand name Imfinzi, approval to treat bladder cancer and some lung cancers.


Tremelimumab has shown a lot of promise as a complement to other cancer treatments, even though it was ineffective on its own in a previous study with mesothelioma. It works by inhibiting a protein known as CTLA-4, which durvalumab does not.


The combination was given intravenously two weeks before the scheduled surgery in the trial. Patients received intraoperative chemotherapy right after surgery.


Mesothelioma study may result in FDA approval Despite advances in immunotherapy for pleural mesothelioma treatment, its efficacy has been inconsistent and limited.


After demonstrating a four-month survival improvement over standard chemotherapy, the FDA granted first-line treatment approval for the immunotherapy combination of Opdivo and Yervoy in 2020.


The multimodal combination of surgery, chemotherapy, and radiation remains the most effective treatment, but the majority of those patients only survive for less than two years. Only a third of people with pleural mesothelioma are even eligible for surgery.


A recent combination of immunotherapy as a pre-surgical treatment has received a lot of attention, bringing the FDA's next approval a little closer.


In patients with MPM, "neoadjuvant ICB" (immune checkpoint blockade) appears to be safe and feasible. It has a potentially beneficial effect on survival and causes pathological tumor responses, the authors concluded.

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