Mesothelioma Clinical Trial Exploring Family Predisposition
The National Cancer Institute has opened a clinical trial using mesothelioma patients and their family members to explore predisposition to the cancer and potential solutions to negating it.
The trial is a follow up to an earlier study of a genetic mutation that creates susceptibility to various cancers but a longer-than-normal survival with platinum-based chemotherapy treatment.
“This is an important, long-term study that could have implications not only for a patient, but for family members, too,” Dr. Raffit Hassan, NCI senior investigator told The Mesothelioma Center at Asbestos.com. “Progress can be made in terms of prevention and early detection.”
Tracking Inherited Mutations
In the clinical trial, Hassan and his staff will be studying mutations of BAP1, a tumor-suppressor gene, and other similar-acting genes.
Children as young as 2 years old will be eligible to participate. Participants who have a confirmed mutation will be encouraged to ask relatives to join the study.
They also will have an option of being in a remote group — providing medical and family history by phone annually — or in a more closely monitored setting that includes blood tests, scans and physical exams.
The mutations also have been associated with renal and basal cell carcinoma, cutaneous melanoma and meningioma.
Relatives identified with the mutations but no cancer emergence would be encouraged to avoid risk factors such as exposure to asbestos and other toxins.
It also could lead to a regular screening process and routine exams for those with the mutation. It potentially could help with early detection of several cancers, when treatment is more effective.
Mutation Produces Survival Benefits
The just-completed study by the NCI focused more on how the genetic mutations of DNA repair genes impact mesothelioma survival.
Proceedings of the National Academy of Sciences published the study in March 2019.
The study included 434 patients with mesothelioma who underwent genetic testing at either the NCI or the University of Chicago Medicine Comprehensive Cancer Center.
Researchers found that 12% of the patients had a mutation of a DNA suppressor gene.
They also found that mesothelioma patients with a loss-of-function gene mutation had a 7.9-year median survival with platinum chemotherapy treatment, compared with a 2.4-year survival for those without the mutation.
Hassan attributed the median survival for both groups to a higher-than-normal percentage of female and younger patients in the study.
Genetic Testing for All Mesothelioma Patients
Routine genetic testing for all mesothelioma patients likely would provide a more accurate prognosis on individual survival, assist in treatment decisions and potentially alert family members to their own susceptibility.
“These findings strongly suggest that every [mesothelioma] patient should be tested,” Hassan said. “These studies take time, but the data suggests we should do that.”
Earlier studies also have shown the loss of function of the BRCA1 and BRCA2 genes — which are related to the BAP1 gene — makes a patient more sensitive to immunotherapy drugs known at PARP inhibitors.
The NCI already is in the midst of another clinical trial involving mesothelioma and olaparib, a PARP inhibitor which has been effective with genetic mutations linked to breast and ovarian cancers.
The University of Florida has an ongoing clinical trial involving niraparib — a drug that targets the BAP1 mutation for four different cancers — including mesothelioma.
“A family member might be at risk, not only for mesothelioma, but also for a more common cancer,” Hassan said. “If we can identify these patients, then family members can be monitored closely.”
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3 Cited Article Sources
ClinicalTrials.gov. (2019, March 21). Long Term Follow-up of Mesothelioma Patients and Their Family Members With Germline Mutations in BAP1 and Other Genes.
Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03830229?term=NCT03830229&rank=1
ClinicalTrials.gov. (2019, May 2). A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001).
Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03207347?term=nct03207347&rank=1
- Hassan, R. et.al. (2019, March 5). Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy. Retrieved from: https://www.pnas.org/content/early/2019/04/10/1821510116.abstract