Chemo Plus Immunotherapy Shows Promise As First-line Treatment for Mesothelioma
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Inoperable malignant pleural mesothelioma, is a rare and aggressive cancer of the protective lining of the lungs, or pleura, often caused by exposure to asbestos. At the annual meeting of the American Society of Clinical Oncology (ASCO), held virtually from May 29-31, 2020, a researcher from the Johns Hopkins Kimmel Cancer Center presented findings from a multicenter study that evaluated the efficacy of an immunotherapy-plus-chemotherapy combination for the disease.
According to Patrick Forde, M.B.B.Ch., associate professor of oncology at the Johns Hopkins University School of Medicine, director of the Kimmel Center's thoracic cancer clinical research program and a Bloomberg~Kimmel Institute for Cancer Immunotherapy investigator, the study looked at 55 patients from 15 U.S. cancer centers who received the immunotherapy drug durvalumab in combination with two anticancer chemotherapies -- cisplatin and pemetrexed -- to create a novel first-line treatment.
Patients received six treatments of the combination therapy every three weeks, followed by treatment with durvalumab alone, for up to one year in total. The chemo-immunotherapy combination improved overall survival to 20.4 months from the historically expected survival of 12 months with chemotherapy alone. This is the first study to show survival times exceeding 20 months for patients with inoperable mesothelioma. The treatment was well-tolerated overall, with no unexpected side effects reported.
"Inflammation is key to the development of pleural mesothelioma and, as such, it represents a key target for immunotherapy. This, in addition to earlier studies that showed promising results using the same immunotherapy drug in previously treated cases, led us to study the combination," says Forde. "Because of the promising results, we are in the process of starting a phase 3 study to confirm the benefit of this approach." This study will begin accruing patients across the United States and Australia in late 2020.
The researchers studied tissue samples from patients who received the combination therapy and found that it prevented a protein called PD-L1 from forming a "protective armor" around cancer cells. The researchers say that's because immunotherapies known as checkpoint blockers, such as durvalumab, act against PD-L1 and therefore, disrupt a cancer cell's ability to avoid detection and destruction by immune cells.
Reference: Forde, et al. (2020) PrE0505: Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (MPM)—A PrECOG LLC study. J Clin Oncol DOI: 10.1200/JCO.2020.38
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