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Investigational Drug Shows Response in Patients with Malignant Pleural Mesothelioma


Cediranib combined with platinum-based chemotherapy helped patients live longer than placebo.

Patients with malignant pleural mesothelioma had better response rates and lived longer without their disease worsening following treatment with cediranib and platinum-based chemotherapy, according to phase 2 study findings published in the Journal of Clinical Oncology.

The trial included 92 patients who never had chemotherapy and whose tumors could not be removed during surgery. Patients were mostly men (85%) and the median age was 72 years. They were enrolled between October 2011 and February 2016.

Patients were chosen randomly to receive either platinum-pemetrexed, a type of chemotherapy, with cediranib or placebo. Cediranib is an oral tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR). It’s still being investigated and, therefore, not approved by the Food and Drug Administration. But works by preventing the growth of new blood vessels that tumors need to grow and may kill cancer cells, according to the National Cancer Institute.

Since it has shown promise in early trials, researchers wanted to evaluate its efficacy in malignant pleural mesothelioma. The primary endpoint was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival, or the length of time during and after treatment that a patient lives without the disease worsening. Secondary end points included areas such as overall survival and safety.

Malignant pleural mesothelioma is a rare disease and has few treatment options. It develops in the cells that form the outer lining of the lungs and inner lining of the chest cavity. Patients may experience shortness of breath and chest pain as early signs of the disease. Asbestos exposure is the main risk factor for developing mesothelioma.

In this study, the researchers found that the chemotherapy/cediranib combination improved progression-free survival of patients compared with placebo (7.2 months versus 5.6 months). The medication also increased modified RECIST v1.1 response. But researchers found no significant difference in overall survival.

“The clinical benefit to cediranib was more pronounced in patients who typically have a worse prognosis, which includes men, patients with prior radiation therapy exposure…,” the researchers wrote.

However, the regimen with cediranib had more treatment-related side effects. These included grades 3 and 4 diarrhea, dehydration, hypertension and weight loss. This group also experienced nausea, peripheral neuropathy and muscle weakness. Four deaths occurred in the trial: two in the cediranib group and two in the placebo group.

“Overall, antiangiogenics seem to provide clinical benefit for a subgroup of patients with malignant pleural mesothelioma,” the researchers wrote. “It is essential that future studies include translational correlates for predictive biomarkers that can identify this population of


They added, “There is clear evidence that the addition of cediranib increased response rates and reduced tumor burden; however, this did not translate into a significant overall survival improvement.”

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