My husband's genetic testing came back with a .51 Tumor Mutational Burden. He has a 66.40% TP53 Allelic Fraction and 45.76% PTEN. His NO said these are common in many cancers and said neither are very actionable.
He was intrigued by the FIG-ROS1 as it usually shows up in small cell lung cancer and with recurrence might be eligible for a bucket trial with entrectinib.
He also has CDKN2A and CDKN2B Copy Loss.
I am just starting to look into what all this means. I have not looked into clinical trials much but am pursuing possibly getting a PD1 Inhibitor although once again I am told he needs recurrence.
He is 7 months out, stopped adjuvant TMZ after 2 rounds, unmethylated, IDH Wildtype, doing Optune, supplements and cannabis oil and overall doing very very well. Thanks.
I presume the 0.5 tumor mutational burden, means 0.5 mutations per megabase of DNA. This is within the normal range for tumors and not hypermutated (not surprising for an untreated specimen).
ReplyDeleteWhat kind of report was this? Foundation, or some other company? Does it give an allelic fraction for the FIG-ROS1 fusion?
Entrectinib has at least a chance of helping as it seems to have been designed with the blood-brain barrier in mind
http://www.medscape.com/viewarticle/862131
However, a single agent approach is unlikely to give durable benefit. For one thing there are surely many tumor cells that don't have this particular genetic alteration, and secondly in the cells that do have it, it is not the only pathway driving the tumor proliferation and survival. The failure of single agent approaches is the whole reason this blog exists*. Personally I would look at more promising clinical trials before any single agent kinase inhibitor trial. Where are you located?
*This doesn't mean I think all kinase inhibitors will have no effect, just that they would best be used as part of a multi-agent approach and not relied on in isolation.
This report was done by a new company called Tempus. This is what they recommend at Northwestern Brain Tumor Institute in Chicago. It does a panel of 1714 genes. It does not give an allelic fraction for the FIG-ROS1.
ReplyDeleteI agree with you about the single agent approach and am just starting to explore clinical trials and how that process works. Our NO has not really mentioned any as everything seems to hinge on recurrence. I have asked about Nivolumab off-label and he said we would probably be denied.
I have also inquired about Val-83 which he knew nothing about. I see there is a trial for newly occurring GBM by DelMar Pharmaceuticals but it seems to be in China. We are 2 hours northwest of Chicago.
There's also an expanded access protocol for VAL-083.
Deletehttps://clinicaltrials.gov/ct2/show/NCT03138629
This also requires relapsed/refractory disease. Would be worth looking into this and getting in touch with the company, since he didn't finish his TMZ cycles and isn't on any other chemotherapy. Seems to me he'd be the ideal candidate for VAL-083 for that reason, and also due to MGMT unmethylated status.
Personally I wouldn't go for single agent nivolumab unless the tumor was hypermutated (which it isn't). PD-1 inhibitors are more exciting in combination with vaccines and viral therapies, but if you use it as a single agent you'd automatically be excluded from those trials.
Thanks Stephen, I will look into it and I appreciate the input about nivolumab.
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