Preoperative immunotherapy for mesothelioma shows favorable results

In a study recently published in the journal Clinical Cancer Research, researchers at Baylor College of Medicine found that treating patients with resectable malignant pleural mesothelioma, meaning their tumor can be surgically removed, with immunotherapy prior to surgery resulted in favorable clinical outcomes. The study lays the foundation for neoadjuvant immunotherapy in mesothelioma.

“Mesothelioma is a devastating, low-survivability disease,” said Dr. Bryan Burt, professor and chief of the David J. Sugarbaker Division of Thoracic Surgery in the Michael E. DeBakey Department of Surgery at Baylor and senior paper author. “Traditionally, this disease has defeated all standard therapies.”

Immune checkpoint inhibitors are drugs that activate the immune system to fight cancer. They have revolutionized the treatment of cancer in general, but their effectiveness in mesothelioma has only recently been recognized. Recent research on the effectiveness of immunotherapy in patients with inoperable mesothelioma showed favorable results, prompting Burt and colleagues to investigate this approach in patients with resectable mesothelioma.

“Surgery itself may not be curative, but combining surgery with another therapy modality often offers benefits,” said Burt, who is also a member of the Dan L. Duncan Comprehensive Cancer Center in Baylor. “Our study is an important step in evaluating whether checkpoint inhibitors are safe and feasible before surgery.”

One reason to administer therapy preoperatively that increases immune reactivity to a tumor is that immunotherapy can activate an immune response that persists after tumor resection. When the tumor tries to come back, the body has an established memory immune response to fight it.

For this study, participants with resectable mesothelioma were divided into two groups. The first received a single cycle of durvalumab, which blocks the PD-L1 checkpoint. The other group received a single course of dual-agent immunotherapy that included durvalumab plus tremelimumab, which blocks the CTLA-4 checkpoint. Both groups received the immunotherapy approximately three weeks prior to surgery.

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Surgeons biopsied the tumor before each treatment, then gave immunotherapy and removed more tissue during the resection process to assess how the drugs affected the tumor’s microenvironment and to see how the drugs modulated the immune cells in the tumor.

The authors found that durvalumab plus tremelimumab combination immunotherapy resulted in significant and beneficial changes in the tumor microenvironment. The dual-drug immunotherapy increased the number of important types of CD8 T cells in the tumor, which serve as ‘soldiers’ in the immune response, killing and remembering the tumor. Although this study was not primarily designed to assess efficacy, a provocative signal was found in the form of prolonged overall survival in the dual-agent immunotherapy group.

Researchers are continuing to track study participants who received the treatment more than three years ago.

As a next step in this research, mesothelioma surgeon Dr. R. Taylor Ripley of Burt and Baylor designed a larger study comparing dual immunotherapy with chemo-immunotherapy.

Other authors of the study are Hyun-Sung Lee, Hee-Jin Jang, Maheshwari Ramineni, Daniel Y. Wang, Daniela Ramos, Jong Min Choi, Taylor Splawn, Monica Espinoza, Michelle Almarez, Leandria Hosey, Eunji Jo, Susan Hilsenbeck, Christopher I Amos and R. Taylor Ripley, all of Baylor College of Medicine.

This work was supported by AstraZeneca, an NIH R37 MERIT Award, a Cancer Prevention and Research Institute of Texas Grant, a Michael E. DeBakey Department of Surgery Seed Grant, and the Gutenstein Family Foundation. This project was also supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH and CPRIT. This research was conducted at the Flow Cytometry & Cellular Imaging Facility, which is supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant CA016672, NCI’s Research Specialist 1 R50 CA243707-01A1, and a Shared Instrumentation Award from the CPRIT RP121010. dr Amos is a CPRIT Research Fellow supported by RR170048.

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