The makers of a VEGF-inhibitor called nintedanib are recruiting patients with unresectable pleural mesothelioma for a Phase III clinical trial of the drug in combination with standard chemotherapy.
The multicenter trial sponsored by drug maker Boehringer Ingelheim will eventually include a total of 450 mesothelioma patients, but preliminary results from the first 87 patients look promising.
According to data presented at the 2017 American Society of Clinical Oncology Annual Meeting, adding nintedanib to pemetrexed and cisplatin improved the progression-free survival of pleural mesothelioma patients by almost four months over placebo.
In a 2016 study that went by the acronym ‘MAPS’, French researchers found that giving another VEGF inhibitor, called bevacizumab, along with pemetrexed and cisplatin lowered the risk of death from malignant mesothelioma by 23 percent.
VEGF’s Role in Mesothelioma
VEGF has been the focus of a number of cancer studies in recent years. The protein stimulates the formation of new blood vessels which are needed to support the growth of mesothelioma tumors.
Emerging evidence also suggests that VEGF may suppress the immune system’s response to malignant mesothelioma and other cancers.
Inhibiting VEGF with drugs like bevacizumab and nintedanib, therefore, may help fight mesothelioma on several levels.
A Boost for Chemotherapy
In the current study, researchers are trying to find out if nintedanib (Ofev) could enhance the effectiveness of mesothelioma chemotherapy like bevacizumab did, but without some of the dose-limiting side effects.
The LUME-Meso trial includes mesothelioma patients who have not yet been treated with chemotherapy. Patients are randomized to receive pemetrexed and cisplatin – the standard mesothelioma drug therapy combination – on the first day with the addition of either nintedanib or a placebo on each day after that.
The full cycle lasts for 21 days and trial participants are eligible to undergo up to six 21-day cycles.
“Patients without disease progression who are eligible to continue study treatment will receive maintenance treatment with nintedanib or placebo until disease progression or undue toxicity,” writes Italian researcher Giorgio Scagliotti of the University of Turin, first author on the study summary in Clinical Lung Cancer.
Researchers will continue to track progression-free survival, the amount of time it takes for mesothelioma tumors to start growing again on the treatment. They are also evaluating the level of disease control and overall mesothelioma survival.
The active Phase III trial is open to patients with confirmed disease who have not had chemotherapy or radiotherapy and are expected to live for at least three months. Patients cannot have significant liver or heart disease. More information can be found at clinicaltrials.gov.
Scagliotti, GV, et al, “LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled Study of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib in Patients With Unresectable Malignant Pleural Mesothelioma”, March 22, 2017, Clinical Lung Cancer, Epub ahead of print.
Levin, PA, and Dowell, JE, “Spotlight on bevacizumab and its potential in the treatment of malignant pleural mesothelioma: the evidence to date”, April 7, 2017, OncoTargets and Therapy, 2057-2066